[ CAS No. 14542-12-2 ] {[proInfo.proName]}

Name: 14542-12-2|Thiazol-2-ylmethanol|95%
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Quality Control of [ 14542-12-2 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 14542-12-2 ]

Product Details of [ 14542-12-2 ]

CAS No. :	14542-12-2	MDL No. :	MFCD06200855
Formula :	C₄H₅NOS	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JNHDLNXNYPLBMJ-UHFFFAOYSA-N
M.W :	115.15	Pubchem ID :	2795213
Synonyms :

Calculated chemistry of [ 14542-12-2 ]

Physicochemical Properties

Num. heavy atoms :	7
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.25
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	28.24
TPSA :	61.36 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.93 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.39
Log Po/w (XLOGP3) :	0.1
Log Po/w (WLOGP) :	0.48
Log Po/w (MLOGP) :	-0.88
Log Po/w (SILICOS-IT) :	2.01
Consensus Log Po/w :	0.62

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.08
Solubility :	9.59 mg/ml ; 0.0833 mol/l
Class :	Very soluble
Log S (Ali) :	-0.94
Solubility :	13.1 mg/ml ; 0.114 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.07
Solubility :	9.85 mg/ml ; 0.0855 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.11

Safety of [ 14542-12-2 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 14542-12-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 14542-12-2 ]
Downstream synthetic route of [ 14542-12-2 ]

[ 14542-12-2 ] Synthesis Path-Upstream 1~8

1
[ 14542-12-2 ]
[ 10200-59-6 ]

Reference： [1] Acta Chemica Scandinavica (1947-1973), 1966, vol. 20, p. 2649 - 2657
[2] Organic Letters, 2006, vol. 8, # 1, p. 167 - 170
[3] Mendeleev Communications, 2010, vol. 20, # 4, p. 185 - 191

2
[ 10200-59-6 ]
[ 14542-12-2 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium tetrahydroborate In methanol at 0℃; for 2 h;	Thiazole-2-carbaldehyde (301 mg, 2.66 mmol) was dissolved in methanol (15 mL) at 0 ° C,Sodium borohydride (151 mg, 3.99 mmol) was added to the system and reacted for 2 h. The reaction solution was poured into water (10 mL)The solvent was spin-dried, extracted with ethyl acetate (15 mL × 3), washed with saturated brine (15 mL), dried over anhydrous sodium sulfate,The solvent was removed and the residue was subjected to column chromatography (eluent:PE / EtOAc (v / v) = 5/1) to give 285 mg of a pale yellow oil, yield: 93percent.
82%	Stage #1: With sodium tetrahydroborate In methanol at 0 - 20℃; for 1 h;	Manufacturing Example 88-1-1 Thiazole-2-yl-methanol; To a mixture of 2-formylthiazole (300 mg, 2.65 mmol) and methanol (30 mL) was added sodium borohydride (201.0 mg, 5.30 mmol) at 0° C., which was stirred for 1 hour at room temperature. Water was added to this reaction mixture, which was then extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (diethyl ether) to obtain the title compound (251.2 mg, 82percent).¹H-NMR Spectrum (DMSO-d₆) δ (ppm): 4.74 (2H, d, J=6.0 Hz), 6.04 (1H, t, J=6.0 Hz), 7.63-7.65 (1H, m), 7.73-7.75 (1H, m).
74%	With sodium tetrahydroborate In methanol at -60℃; for 2 h;	A stirred and cooled (-60 °C) sol. of thiazole-2-carbaldehyde (3.97 g, 35.1 mmol) in MeOH (35 mL) was treated with NaBH4 (1.33 g, 35.1 mmol). The reaction mixture was stirred at -60 °C for 2 h, then carefully quenched with acetone (2.7 mL), and allowed to warm to rt. The solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc) yielded the title compound (3 g, 74percent) as an orange oil that crystallized at -20 °C, and remained a solid upon warming to rt. LC-MS: tR = 0.26 min, ES+: 116.13.

74%	at -60℃; for 2 h;	A stirred and cooled (-60 ⁰C) sol. of thiazole-2-carbaldehyde (3.97 g, 35.1 mmol) in MeOH (35 mL) was treated with NaBH₄ (1.33 g, 35.1 mmol). The reaction mixture was stirred at -60 ⁰C for 2 h, then carefully quenched with acetone (2.7 mL), warmed to rt, and the solvents were removed in vacuo. Purification of the crude by FC (EtOAc) yielded the title compound (3.00 g, 74percent) as an orange oil that crystallized at -20 ⁰C and remained a solid upon warming to rt.
66%	Stage #1: With sodium tetrahydroborate In methanol at 0℃; Stage #2: With water In methanol	Referential Example 12: thiazole-2-methanol While stirring under ice cooling, sodium borohydride (242 mg, 6.40 mmol) was added to a methanol (10 ml) solution of 2-formylthiazole (483 mg, 4.27 mmol).. After completion of the reaction was confirmed, water was added to the reaction mixture.. The resulting mixture was concentrated under reduced pressure.. Water and ethyl acetate were added to the residue to separate the organic layer.. The organic layer was washed with brine and then dried over anhydrous sodium sulfate.. After filtration, the filtrate was concentrated under reduced pressure.. The residue was subjected to chromatography on a silica gel column.. The fraction obtained from the hexane:ethyl acetate (=1:1) elude was concentrated under reduced pressure, whereby the title compound (324 mg, 66percent) was obtained as a white solid.1H-NMR (400MHz, CDCl3) δ: 3.30-3.70(1H,m), 5.14(2H,s), 7.32(1H,d,J=3.4Hz), 7.74(1H,d,J=3.2Hz). MS (m/z): 116 (M++H).
62%	With sodium hydroxide; sodium tetrahydroborate In methanol	b. 2-(Hydroxymethyl)thiazole To a cooled solution (0° C.) of 2-formylthiazole (described in example 71a) (1.50 g, 13.27 mmol) in methanol (25 mL) under nitrogen was added sodium borohydride (0.300 g, 7.94 mmol). After the addition was complete, the reaction was warmed to room temperature over 1 h and stirred at room temperature for 3 h. Excess reagent was quenched with acetone (10 mL) and stirred 18 h. The reaction was acidified with 3N HCl (25 mL), cooled to 0° C. and rebasified with 2.5N NaOH (40 mL). The aqueous phase was extracted with ethyl acetate (3*25 mL). Combined organic extracts were dried over anhydrous magnesium sulfate, filtered and reduced to a relatively pure oil in 62percent yield. TLC analysis (R_f 0.15, 40percent ethyl acetate in hexane). No further purification was required. MS (CI, CH4) m/z 116 (M+1,82), 144 (M+29,17), 98 (100).
60%	With sodium borohydrid In methanol	Example 391A 1,3-thiazol-2-ylmethanol To thiazole-2-carbaldehyde (1133 mg, 1 mmol) in methanol (10 mL) was added sodium borohydride (41 mg, 1.2 mmol) portion wise at 0° C. The mixture was stirred at room temperature for 2 hours. The mixture was diluted with water and acidified to pH 3 with 1M hydrochloric acid, and extracted with ethyl acetate (2*50 mL). The organic layers were washed with saturated aqueous sodium bicarbonate, water, brine, dried over magnesium sulfate, filtered and concentrated to give the title compound (69 mg, 60percent).
58%	With sodium tetrahydroborate In methanol at 0℃; for 3 h;	Aldehyde 3 (5.8 g, 51.3 mmol, 1 eq)/10 mL methanol was treated with NaBH₄ (2.1 g,1.1 eq) at 0 °C for 3 h. The solvent was removed and EtOAc was added forextraction. Flash chromatography (2:1 Hexane : EtOAc) provided 3.4 g of the desiredproduct (58 percent yield).¹H NMR (CDCI₃ 8): 4.90 (s, 2H) 7.27 (m, 1H) 7.70
56%	Stage #1: With sodium tetrahydroborate In ethanol for 16 h; Heating / reflux Stage #2: With water In ethyl acetate	0.20 ml (2.28 mmol) 2-thiazolecarboxaldehyde are placed in 10 ml of ethanol, 0.172 g (4.55 mmol) sodium borohydride are added. The reaction mixture is refluxed for 16 hours with stirring, then concentrated by evaporation. The residue is extracted with water and ethyl acetate, the organic phase is washed with water. The combined aqueous phases are saturated with sodium chloride and extracted with ethyl acetate. The resulting organic phase is dried and evaporated to dryness. Yield: 0.146 g (=56percent of theoretical)
56%	Stage #1: With sodium tetrahydroborate In ethanol at 20℃; for 16 h; Heating / reflux Stage #2: With water In ethyl acetate	Precursor for compound 17: thiazol-2-yl-methanol 0.20 ml (2.28 mmol) 2-thiazol-carboxaldehyde are placed in 10 ml of ethanol at ambient temperature, 172 mg (4.55 mmol) sodium borohydride are added and then the mixture is refluxed for 16 hours with stirring. Then the reaction mixture is concentrated by evaporation, the residue is extracted with water and ethyl acetate. The aqueous phase is saturated with sodium chloride and extracted again with ethyl acetate. The resulting organic phase is dried and evaporated to dryness. Yield: 146 mg (=56percent of theoretical)
53%	Stage #1: With sodium tetrahydroborate In ethanol at 20℃; for 1.5 h; Stage #2: With water In ethanol	Sodium borohydride (0.17 g, 4.49 mmol) was added to a solution * of 2- thiazolecarboxaldehyde (0.39 mL, 4.44 mmol) in ethanol (25 mL). After stirring for 1.5 h at room temperature, the reaction was quenched with water and concentrated. The residue was dissolved in ethyl acetate and washed with water and brine, dried over magnesium sulfate and concentrated to give 0.27 g, (53percent) of thiazol-2-yl-methanol as a tan oil which had: NMR (CDCI₃) δ 7.72 (d, J = 3.3 Hz, 1 H), 7.31 (d, J = 3.3 Hz, 1 H), 4.95 9s, 2H); 2.83 (br s, 1 H). This was mixed with triethyl amine (0.33 mL, 2.37 mmol) in methylene chloride (4 mL) and cooled in ice. Methanesulfonylchloride (0.18 mL, 2.33 mmol) in methylene chloride (2mL) was added dropwise over 1 min. After 30 min stirring at O⁰C, the reaction was washed with water and brine, dried over magnesium sulfate and concentrated to yield 0.41 g (91 percent) of methanesulfonic acid thiazol-2-ylmethyl ester as an orange oil which had: NMR (CDCI₃) δ 7.83 (d, J = 3.3 Hz, 1 H), 7.45 (d, J = 3.3 Hz, 1 H), 5.50 (s, 2H), 3.06 (s, 3H).
16.4%	With sodium tetrahydroborate In methanol at -60℃; for 1 h; Inert atmosphere	To a solution of n-BuLi (8.4 ml, 1.6 mol/l, 13.4 mmol) in THF (30 mL) was added 2-bromothiazole (377 mg, 2.12 mmol) dropwise under nitrogen atmosphere at -70° C., and the mixture was stirred at the temperature for 1 h. Then DMF (1.4 ml, 18.3 mmol) was added into the solution dropwise under nitrogen atmosphere at -70° C. The resulting mixture was stirred at the temperature for 1 h. Then the mixture was quenched with aqueous saturated ammonium chloride, diluted with ethyl acetate and water, and the phases were separated. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give yellow oil. The yellow oil was dissolved in methanol (15 ml), cooled to -60° C., and sodium borohydride (463 mg, 12.2 mmol) was added portionwise under nitrogen atmosphere. The mixture was stirred at the temperature for 1 h. The reaction was quenched with acetone and concentrated. The residue was diluted with ethyl acetate and water, and the phases were separated. The organic layer was dried over sodium sulfate, filtered and concentrated, then purified by silica gel chromatography eluting with petroleum/ethyl acetate=3:1 to give thiazol-2-ylmethanol (230 mg, 16.4percent yield) as brown oil. LCMS MH⁺ 116.
15.2%	With sodium tetrahydroborate In methanol at 0℃; for 2 h;	To a solution of 18a (20.55 g, 0.18 mol) in MeOH (100 mL) was added NaBH₄ (7.6 g, 0.20 mol) at 0°C. The reaction mixture was stirred at 0°C for 2 hours and monitored using TLC. Then, acetone (20 mL) was added into the solution and stirred for 20 minutes and the mixture was concentrated in vacuo. After that, the residue was washed with water (200 mL) and extracted with ethyl acetate (300 mL), washed with brine and dried over anhydrous sodium sulfate. After concentration in vacuo, and the resutling residue was purified using Si0₂ chromatography, eluting with petroleum ether: ethyl acetate (10/1-1/1) to provide 18b (3.18 g, 15.2percent)
15.2%	With sodium tetrahydroborate In methanol at 0℃; for 2 h;	To a solution of 18a (20.55 g, 0.18 mol) in MeOH (100 mL) was added NaBH₄ (7.6 g, 0.20 mol) at 0°C. The reaction mixture was stirred at 0°C for 2 hours and monitored using TLC. Then, acetone (20 mL) was added into the solution and stirred for 20 minutes and the mixture was concentrated in vacuo. After that, the residue was washed with water (200 mL) and extracted with ethyl acetate (300 mL), washed with brine and dried over anhydrous sodium sulfate. After concentration in vacuo, the residue was purified using Si0₂ chromatography, eluting with petroleum ether: ethyl acetate (10/1-1/1) to provide 18b (3.18 g, 15.2percent).
12 g	With sodium tetrahydroborate In methanol at 0 - 20℃;	To a mixture of 2-formylthiazole (84.22g, 0.75mol) and methanol (100 mL) was added sodium borohydride (120g, 1.5mol) at 0°C, which was stirred for overnight at room temperature. Water was added to this reaction mixture, which was then extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography with DCM/MeOH (100:1-50:1) to afford thiazol-2-ylmethanol as light yellow oil (12 g ,14percent).
230 mg	at -60℃; for 1 h; Inert atmosphere	Step 1 thiazol-2-ylmethanol To a solution of n-BuLi (8.4 ml , 1.6 mol/1 , 13.4 mmol) in THF (30 mL) was added 2- bromothiazole (377 mg, 2.12 mmol) dropwise under nitrogen atmosphere at -70 °C, and the mixture was stirred at the temperature for 1 h. Then DMF (1.4 ml, 18.3 mmol) was added into the solution dropwise under nitrogen atmosphere at -70 °C. The resulting mixture was stirred at the temperature for 1 h. Then the mixture was quenched with aqueous saturated ammonium chloride, diluted with ethyl acetate and water, and the phases were separated. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give yellow oil. The yellow oil was dissolved in methanol (15 ml) , cooled to -60 °C, ans sodium borohydride (463 mg , 12.2 mmol) was added portionwise under nitrogen atmosphere. The mixture was stirred at the temperature for 1 h. The reaction was quenched with acetone and concentrated. The residue was diluted with ethyl acetate and water, and the phases were separated. The organic layer was dried over sodium sulfate, filtered and concentrated, then purified by silica gel chromatography eluting with petroleum/ ethyl acetate= 3: 1 to give thiazol-2-ylmethanol (230 mg, 16.4 percent yield) as brown oil . LCMS MH⁺ 1 16.

Reference： [1] Chinese Journal of Chemistry, 2014, vol. 32, # 6, p. 538 - 544
[2] Patent: CN106749268, 2017, A, . Location in patent: Paragraph 0798; 0799
[3] European Journal of Organic Chemistry, 2017, vol. 2017, # 33, p. 4972 - 4983
[4] Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, 2007, vol. 62, # 12, p. 1525 - 1529
[5] Tetrahedron, 1988, vol. 44, # 7, p. 2021 - 2032
[6] Patent: US2009/82403, 2009, A1, . Location in patent: Page/Page column 147-148
[7] Patent: WO2006/21402, 2006, A1, . Location in patent: Page/Page column 36
[8] Patent: WO2006/92268, 2006, A1, . Location in patent: Page/Page column 22-23
[9] Patent: EP1466898, 2004, A1, . Location in patent: Page 90
[10] Patent: US5512575, 1996, A,
[11] Patent: US2004/162285, 2004, A1,
[12] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 17, p. 4845 - 4850
[13] Patent: WO2006/19957, 2006, A2, . Location in patent: Page/Page column 25
[14] Patent: US2006/116372, 2006, A1, . Location in patent: Page/Page column 7
[15] Patent: US2006/116372, 2006, A1, . Location in patent: Page/Page column 7
[16] Patent: WO2007/34277, 2007, A1, . Location in patent: Page/Page column 55
[17] Patent: US2014/275528, 2014, A1, . Location in patent: Paragraph 0304; 0305
[18] Patent: WO2014/110705, 2014, A1, . Location in patent: Page/Page column 75
[19] Patent: WO2014/110687, 2014, A1, . Location in patent: Page/Page column 56
[20] Journal of Organic Chemistry, 1995, vol. 60, # 15, p. 4749 - 4754
[21] Journal of Materials Chemistry, 1998, vol. 8, # 4, p. 833 - 835
[22] Patent: WO2006/46031, 2006, A1, . Location in patent: Page/Page column 76-77
[23] Patent: US2009/170907, 2009, A1, . Location in patent: Page/Page column 60
[24] Patent: EP1422228, 2004, A1, . Location in patent: Page 221
[25] Patent: EP1443041, 2004, A1, . Location in patent: Page 27
[26] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 24, p. 7414 - 7420
[27] Patent: WO2013/80222, 2013, A1, . Location in patent: Page/Page column 33
[28] Patent: WO2014/66795, 2014, A1, . Location in patent: Paragraph 0174 - 0175
[29] Patent: WO2014/143799, 2014, A2, . Location in patent: Page/Page column 386; 387
[30] Patent: US2016/137639, 2016, A1, . Location in patent: Paragraph 3410

3
[ 288-47-1 ]
[ 14542-12-2 ]

Reference： [1] Patent: US5821246, 1998, A,

4
[ 14527-42-5 ]
[ 14542-12-2 ]

Reference： [1] Tetrahedron, 1988, vol. 44, # 7, p. 2021 - 2032

5
[ 54101-88-1 ]
[ 14542-12-2 ]

Reference： [1] Tetrahedron, 1991, vol. 47, # 16, p. 2851 - 2860

6
[ 16733-85-0 ]
[ 14542-12-2 ]

Reference： [1] Acta Chemica Scandinavica (1947-1973), 1967, vol. 21, p. 389 - 396

7
[ 288-47-1 ]
[ 50-00-0 ]
[ 14542-12-2 ]

Reference： [1] J. Gen. Chem. USSR (Engl. Transl.), 1961, vol. 31, p. 1255 - 1259[2] Zhurnal Obshchei Khimii, 1961, vol. 31, p. 1356 - 1361

8
[ 40610-14-8 ]
[ 50-00-0 ]
[ 14542-12-2 ]

Reference： [1] Acta Chemica Scandinavica (1947-1973), 1966, vol. 20, p. 2649 - 2657

[ 14542-12-2 ] Synthesis Path-Downstream 1~49

1
[ 288-47-1 ]
[ 50-00-0 ]
[ 14542-12-2 ]

Reference： [1]Journal of general chemistry of the USSR,1961,vol. 31,p. 1255 - 1259
Zhurnal Obshchei Khimii,1961,vol. 31,p. 1356 - 1361

2
[ 40610-14-8 ]
[ 50-00-0 ]
[ 14542-12-2 ]

Reference： [1]Acta Chemica Scandinavica (1947),1966,vol. 20,p. 2649 - 2657

3
[ 14542-12-2 ]
[ 10200-59-6 ]

Reference： [1]Acta Chemica Scandinavica (1947),1966,vol. 20,p. 2649 - 2657
[2]Organic Letters,2006,vol. 8,p. 167 - 170
[3]Mendeleev Communications,2010,vol. 20,p. 185 - 191

4
[ 14542-12-2 ]
[ 3364-78-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With thionyl chloride; In dichloromethane; at 0℃; for 3h;Reflux;	To a 0 oc solution of thiazol-2-ylmethanol (5.80 g, 50.4 mmol) in DCM (100 mL) wasadded slowly thionyl chloride (12.00 g, 101 mmol). After the addition, the mixture was heated torefulx and stirred for 3 h. The reaction mixture was cooled to rt and concentrated in vacuo togive the title compound as brown oil (6.70 g, 100 % ), which was used in the next step withoutfurther purification.
95%	With thionyl chloride; In dichloromethane; at 0℃; for 5h;	To a solution of <strong>[14542-12-2]2-(hydroxymethyl)thiazole</strong> (500 mg, 4.3 mmol) in DCM (25 mL) at 0C was added dropwise thionyl chloride (4.4 mL, 60.8 mmol). After stirring for 5 h, the solution was concentrated in vacuo. The resulting solid was triturated with Et.20 (20 mL x 2) to provide the title compound as a yellow solid (550 mg, 4.1 mmol, 95%).
86.79%	With thionyl chloride; In dichloromethane; for 4h;	Thiazol-2-ylmethanol (287 mg, 2.49 mmol) and thionyl chloride (0.9 mL, 10 mmol) were dissolved in diMethyl chloride (15 mL) and reacted for 4 h. The reaction solution was poured into water (30 mL), extracted with ethyl acetate (30 mL × 3), and saturated brineWashed (15 mL) and dried over anhydrous sodium sulfate. The solvent was removed and the residue was subjected to column chromatography (eluent: PE / EtOAc (v / v) =10/1) to give 289 mg of a pale yellow oil, yield: 86.79%.

76%		Manufacturing Example 88-1-2 2-Chloromethyl-thiazole; To a mixture of thiazole-2-yl-methanol (251 mg, 2.18 mmol) described in Manufacturing Example 88-1-1 and dichloromethane (10 mL) was added thionyl chloride (191 muL, 2.62 mmol) at room temperature, which was stirred for 30 minutes. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, which was then extracted with dichloromethane. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure to obtain the title compound (220.5 mg, 76%).1H-NMR Spectrum (DMSO-d6) delta (ppm): 5.11 (2H, s), 7.81-7.83 (2H, m).
61%	With thionyl chloride; In dichloromethane; at 25℃;	To a solution of thiazol-2-ylmethanol (7.0g, 0.06mol) in dichloromethane (10 mL) was added thionyl chloride (10.85g, 0.09mol). The resulting solution was stirred for 3 h at 25C in a water/ice bath. The reaction was then quenched by the addition of 50 mL of water/ice. The pH value of the solution was adjusted to 7-8 with sodium carbonate (19 %). The resulting solution was extracted with 3x50 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated in vacuo to afford 2-(chloromethyl)-l , 3-thiazole as a crude dark red oil (5 g, 61%).
	With thionyl chloride; In dichloromethane;	Example 391B 2-(chloromethyl)-1,3-thiazole The product of Example 391A (66 mg, 0.57 mmol) was added dropwise into thionyl chloride (0.2 mL, 2.7 mmol) in dichloromethane (9 mL) keeping the temperature at 25 C. The mixture was refluxed for 2 hours. The solvent was evaporated to give the title compound (quantitative yield).
		B. 2-(Chloromethyl)-1,3-thiazole A slurry of <strong>[14542-12-2]1,3-thiazol-2-ylmethanol</strong> (0.542 g, 4.71 mmol) in CCl4/toluene (1:1, 16 mL) was heated to 60 C. until complete dissolution was realized (ca. 10 min). The solution was cooled to rt, PPh3 (1.85 g, 7.07 mmol) was added in one portion, and the mixture was brought to reflux under N2. After 2 h, the mixture was cooled to rt and filtered through a pad of Celite. The filtrate was concentrated in vacuo and purified by flash chromatography (EtOAc/hexanes), affording 0.315 g of the title compound as a colorless oil: 1H NMR (400 MHz, CDCl3) delta 7.77 (d, J=3.2 Hz, 1H), 7.39 (d, J=3.2 Hz, 1H), 4.88 (s, 2H).
	With tetrachloromethane; triphenylphosphine; In benzene; at 95℃; for 2h;	EXAMPLE 20; Compound 20; N-(2-Hydroxymethylthiazolo[5,4-b]pyrid-6-yl)-5-trifluoromethyl-1-[(thiazol-2-yl)methyl]-1H-indole-2-carboxamide; 20.1 2-(Chloromethyl)thiazole; To a solution of 0.5 g (4.34 mmol) of thiazol-2-ylmethanol in 5 mL of carbon tetrachloride and 6 mL of benzene are added 1.71 g (6.51 mmol) of triphenylphosphine. The reaction mixture is stirred at 95 C. for 2 hours. After cooling to room temperature, the reaction mixture is diluted with dichloromethane and then filtered through Celite. The filtrate is concentrated under reduced pressure and the residue obtained is purified by flash chromatography on a column of silica gel, eluting with a mixture of hexane and ethyl acetate, to give 0.4 g of the expected 2-(chloromethyl)thiazole in the form of a pale yellow oil.1H NMR (DMSO D6), delta (ppm): 7.83-7.80 (m, 2H); 5.11 (s, 2H).
	With thionyl chloride; In dichloromethane; at 20℃; for 0.5h;	(i) NaBH4, eOH, 20-35C , 4h; (ii) SOCI2, DC , 20C, 0.5h; (iii) Pd(dppf)2Cl2, K2C03, DMF, 1 10C, 14h; (iv) CF3COOH, CH2C12, 20-35C, 2h; (v) Acryloyl chloride, triethylamine, CH2C12, 20-35C, 16h. (Rcf. for step-(i-ii): US2009/082403)
	With thionyl chloride; In dichloromethane; at 0 - 20℃; for 1h;	Step 2 2-(chloromethyl)thiazole To a solution of thiazol-2-ylmethanol (230 mg, 2.0 mmol)in DCM (5 mL) was added thionyl chloride (0.19 ml, 2.6 mmol) at 0 C and the mixture was stirred at room temperature for 1 h. The mixture was diluted with DCM and water, and the phases were separated. The organic layer was dried over sodium sulfate, filtered and concentrated to give 2-(chloromethyl)thiazole (240 mg, crude), which was used without purification.
	With thionyl chloride; In dichloromethane; at 0 - 20℃; for 1h;	To a solution of thiazol-2-ylmethanol (230 mg, 2.0 mmol) in DCM (5 mL) was added thionyl chloride (0.19 ml, 2.6 mmol) at 0 C. and the mixture was stirred at room temperature for 1 h. The mixture was diluted with DCM and water, and the phases were separated. The organic layer was dried over sodium sulfate, filtered and concentrated to give 2-(chloromethyl)thiazole (240 mg, crude), which was used without purification.

Reference： [1]Patent: WO2018/108125,2018,A1 .Location in patent: Paragraph 00541
[2]Tetrahedron,1988,vol. 44,p. 2021 - 2032
[3]Patent: WO2017/93543,2017,A2 .Location in patent: Page/Page column 101
[4]Patent: CN106749268,2017,A .Location in patent: Paragraph 0801; 0802
[5]Patent: US2009/82403,2009,A1 .Location in patent: Page/Page column 148
[6]Patent: WO2014/66795,2014,A1 .Location in patent: Paragraph 0174 - 0175
[7]Journal of general chemistry of the USSR,1961,vol. 31,p. 1255 - 1259
Zhurnal Obshchei Khimii,1961,vol. 31,p. 1356 - 1361
[8]Journal of Materials Chemistry,1998,vol. 8,p. 833 - 835
[9]Patent: US2004/162285,2004,A1
[10]Patent: US2009/170907,2009,A1 .Location in patent: Page/Page column 60
[11]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7414 - 7420
[12]Patent: US2011/9400,2011,A1 .Location in patent: Page/Page column 17
[13]Patent: WO2013/80222,2013,A1 .Location in patent: Page/Page column 33
[14]Patent: WO2014/143799,2014,A2 .Location in patent: Page/Page column 386; 387
[15]Patent: US2014/275528,2014,A1 .Location in patent: Paragraph 0306; 0307

5
[ 16733-85-0 ]
[ 14542-12-2 ]

Reference： [1]Acta Chemica Scandinavica (1947),1967,vol. 21,p. 389 - 396

6
[ 10200-59-6 ]
[ 14542-12-2 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium tetrahydroborate; In methanol; at 0℃; for 2h;	Thiazole-2-carbaldehyde (301 mg, 2.66 mmol) was dissolved in methanol (15 mL) at 0 C,Sodium borohydride (151 mg, 3.99 mmol) was added to the system and reacted for 2 h. The reaction solution was poured into water (10 mL)The solvent was spin-dried, extracted with ethyl acetate (15 mL × 3), washed with saturated brine (15 mL), dried over anhydrous sodium sulfate,The solvent was removed and the residue was subjected to column chromatography (eluent:PE / EtOAc (v / v) = 5/1) to give 285 mg of a pale yellow oil, yield: 93%.
82%		Manufacturing Example 88-1-1 Thiazole-2-yl-methanol; To a mixture of 2-formylthiazole (300 mg, 2.65 mmol) and methanol (30 mL) was added sodium borohydride (201.0 mg, 5.30 mmol) at 0 C., which was stirred for 1 hour at room temperature. Water was added to this reaction mixture, which was then extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (diethyl ether) to obtain the title compound (251.2 mg, 82%).1H-NMR Spectrum (DMSO-d6) delta (ppm): 4.74 (2H, d, J=6.0 Hz), 6.04 (1H, t, J=6.0 Hz), 7.63-7.65 (1H, m), 7.73-7.75 (1H, m).
74%	With sodium tetrahydroborate; In methanol; at -60℃; for 2h;	A stirred and cooled (-60 C) sol. of thiazole-2-carbaldehyde (3.97 g, 35.1 mmol) in MeOH (35 mL) was treated with NaBH4 (1.33 g, 35.1 mmol). The reaction mixture was stirred at -60 C for 2 h, then carefully quenched with acetone (2.7 mL), and allowed to warm to rt. The solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc) yielded the title compound (3 g, 74%) as an orange oil that crystallized at -20 C, and remained a solid upon warming to rt. LC-MS: tR = 0.26 min, ES+: 116.13.

74%	With methanol; sodium tetrahydroborate; at -60℃; for 2h;	A stirred and cooled (-60 0C) sol. of thiazole-2-carbaldehyde (3.97 g, 35.1 mmol) in MeOH (35 mL) was treated with NaBH4 (1.33 g, 35.1 mmol). The reaction mixture was stirred at -60 0C for 2 h, then carefully quenched with acetone (2.7 mL), warmed to rt, and the solvents were removed in vacuo. Purification of the crude by FC (EtOAc) yielded the title compound (3.00 g, 74%) as an orange oil that crystallized at -20 0C and remained a solid upon warming to rt.
66%		Referential Example 12: thiazole-2-methanol While stirring under ice cooling, sodium borohydride (242 mg, 6.40 mmol) was added to a methanol (10 ml) solution of 2-formylthiazole (483 mg, 4.27 mmol).. After completion of the reaction was confirmed, water was added to the reaction mixture.. The resulting mixture was concentrated under reduced pressure.. Water and ethyl acetate were added to the residue to separate the organic layer.. The organic layer was washed with brine and then dried over anhydrous sodium sulfate.. After filtration, the filtrate was concentrated under reduced pressure.. The residue was subjected to chromatography on a silica gel column.. The fraction obtained from the hexane:ethyl acetate (=1:1) elude was concentrated under reduced pressure, whereby the title compound (324 mg, 66%) was obtained as a white solid.1H-NMR (400MHz, CDCl3) delta: 3.30-3.70(1H,m), 5.14(2H,s), 7.32(1H,d,J=3.4Hz), 7.74(1H,d,J=3.2Hz). MS (m/z): 116 (M++H).
62%	With sodium hydroxide; sodium tetrahydroborate; In methanol;	b. 2-(Hydroxymethyl)thiazole To a cooled solution (0 C.) of 2-formylthiazole (described in example 71a) (1.50 g, 13.27 mmol) in methanol (25 mL) under nitrogen was added sodium borohydride (0.300 g, 7.94 mmol). After the addition was complete, the reaction was warmed to room temperature over 1 h and stirred at room temperature for 3 h. Excess reagent was quenched with acetone (10 mL) and stirred 18 h. The reaction was acidified with 3N HCl (25 mL), cooled to 0 C. and rebasified with 2.5N NaOH (40 mL). The aqueous phase was extracted with ethyl acetate (3*25 mL). Combined organic extracts were dried over anhydrous magnesium sulfate, filtered and reduced to a relatively pure oil in 62% yield. TLC analysis (Rf 0.15, 40% ethyl acetate in hexane). No further purification was required. MS (CI, CH4) m/z 116 (M+1,82), 144 (M+29,17), 98 (100).
60%	With sodium borohydrid; In methanol;	Example 391A 1,3-thiazol-2-ylmethanol To thiazole-2-carbaldehyde (1133 mg, 1 mmol) in methanol (10 mL) was added sodium borohydride (41 mg, 1.2 mmol) portion wise at 0 C. The mixture was stirred at room temperature for 2 hours. The mixture was diluted with water and acidified to pH 3 with 1M hydrochloric acid, and extracted with ethyl acetate (2*50 mL). The organic layers were washed with saturated aqueous sodium bicarbonate, water, brine, dried over magnesium sulfate, filtered and concentrated to give the title compound (69 mg, 60%).
58%	With sodium tetrahydroborate; In methanol; at 0℃; for 3h;	Aldehyde 3 (5.8 g, 51.3 mmol, 1 eq)/10 mL methanol was treated with NaBH4 (2.1 g,1.1 eq) at 0 C for 3 h. The solvent was removed and EtOAc was added forextraction. Flash chromatography (2:1 Hexane : EtOAc) provided 3.4 g of the desiredproduct (58 % yield).1H NMR (CDCI3 8): 4.90 (s, 2H) 7.27 (m, 1H) 7.70 <m, 1H)
56%		0.20 ml (2.28 mmol) 2-thiazolecarboxaldehyde are placed in 10 ml of ethanol, 0.172 g (4.55 mmol) sodium borohydride are added. The reaction mixture is refluxed for 16 hours with stirring, then concentrated by evaporation. The residue is extracted with water and ethyl acetate, the organic phase is washed with water. The combined aqueous phases are saturated with sodium chloride and extracted with ethyl acetate. The resulting organic phase is dried and evaporated to dryness. Yield: 0.146 g (=56% of theoretical)
56%		Precursor for compound 17: thiazol-2-yl-methanol 0.20 ml (2.28 mmol) 2-thiazol-carboxaldehyde are placed in 10 ml of ethanol at ambient temperature, 172 mg (4.55 mmol) sodium borohydride are added and then the mixture is refluxed for 16 hours with stirring. Then the reaction mixture is concentrated by evaporation, the residue is extracted with water and ethyl acetate. The aqueous phase is saturated with sodium chloride and extracted again with ethyl acetate. The resulting organic phase is dried and evaporated to dryness. Yield: 146 mg (=56% of theoretical)
53%		Sodium borohydride (0.17 g, 4.49 mmol) was added to a solution * of 2- thiazolecarboxaldehyde (0.39 mL, 4.44 mmol) in ethanol (25 mL). After stirring for 1.5 h at room temperature, the reaction was quenched with water and concentrated. The residue was dissolved in ethyl acetate and washed with water and brine, dried over magnesium sulfate and concentrated to give 0.27 g, (53%) of thiazol-2-yl-methanol as a tan oil which had: NMR (CDCI3) delta 7.72 (d, J = 3.3 Hz, 1 H), 7.31 (d, J = 3.3 Hz, 1 H), 4.95 9s, 2H); 2.83 (br s, 1 H). This was mixed with triethyl amine (0.33 mL, 2.37 mmol) in methylene chloride (4 mL) and cooled in ice. Methanesulfonylchloride (0.18 mL, 2.33 mmol) in methylene chloride (2mL) was added dropwise over 1 min. After 30 min stirring at O0C, the reaction was washed with water and brine, dried over magnesium sulfate and concentrated to yield 0.41 g (91 %) of methanesulfonic acid thiazol-2-ylmethyl ester as an orange oil which had: NMR (CDCI3) delta 7.83 (d, J = 3.3 Hz, 1 H), 7.45 (d, J = 3.3 Hz, 1 H), 5.50 (s, 2H), 3.06 (s, 3H).
16.4%	With sodium tetrahydroborate; In methanol; at -60℃; for 1h;Inert atmosphere;	To a solution of n-BuLi (8.4 ml, 1.6 mol/l, 13.4 mmol) in THF (30 mL) was added 2-bromothiazole (377 mg, 2.12 mmol) dropwise under nitrogen atmosphere at -70 C., and the mixture was stirred at the temperature for 1 h. Then DMF (1.4 ml, 18.3 mmol) was added into the solution dropwise under nitrogen atmosphere at -70 C. The resulting mixture was stirred at the temperature for 1 h. Then the mixture was quenched with aqueous saturated ammonium chloride, diluted with ethyl acetate and water, and the phases were separated. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give yellow oil. The yellow oil was dissolved in methanol (15 ml), cooled to -60 C., and sodium borohydride (463 mg, 12.2 mmol) was added portionwise under nitrogen atmosphere. The mixture was stirred at the temperature for 1 h. The reaction was quenched with acetone and concentrated. The residue was diluted with ethyl acetate and water, and the phases were separated. The organic layer was dried over sodium sulfate, filtered and concentrated, then purified by silica gel chromatography eluting with petroleum/ethyl acetate=3:1 to give thiazol-2-ylmethanol (230 mg, 16.4% yield) as brown oil. LCMS MH+ 116.
15.2%	With sodium tetrahydroborate; In methanol; at 0℃; for 2h;	To a solution of 18a (20.55 g, 0.18 mol) in MeOH (100 mL) was added NaBH4 (7.6 g, 0.20 mol) at 0C. The reaction mixture was stirred at 0C for 2 hours and monitored using TLC. Then, acetone (20 mL) was added into the solution and stirred for 20 minutes and the mixture was concentrated in vacuo. After that, the residue was washed with water (200 mL) and extracted with ethyl acetate (300 mL), washed with brine and dried over anhydrous sodium sulfate. After concentration in vacuo, and the resutling residue was purified using Si02 chromatography, eluting with petroleum ether: ethyl acetate (10/1-1/1) to provide 18b (3.18 g, 15.2%)
15.2%	With sodium tetrahydroborate; In methanol; at 0℃; for 2h;	To a solution of 18a (20.55 g, 0.18 mol) in MeOH (100 mL) was added NaBH4 (7.6 g, 0.20 mol) at 0C. The reaction mixture was stirred at 0C for 2 hours and monitored using TLC. Then, acetone (20 mL) was added into the solution and stirred for 20 minutes and the mixture was concentrated in vacuo. After that, the residue was washed with water (200 mL) and extracted with ethyl acetate (300 mL), washed with brine and dried over anhydrous sodium sulfate. After concentration in vacuo, the residue was purified using Si02 chromatography, eluting with petroleum ether: ethyl acetate (10/1-1/1) to provide 18b (3.18 g, 15.2%).
	With sodium tetrahydroborate;	148 6-((3R.5SV3.5-Dimethyl-4-thiazol-2-ylmethyl-rhoirhoerazin-l-ylmethvn-2-(lH- indazol-4-yl)-4-morpholin-4- yl-thieno [3.2-d]p yrimidine.Via 2-chloro-6-((3R,5 S)-3 ,5 -dimethyl-4-thiazol-2-ylmethyl-piperazin- 1 - ylmethyl)-4-mophiholin-4-yl-thieno[3,2-d]pyrimidine, prepared from (2R,6S)-2,6- dimethyl- 1 -thiazol-2-ylmethyl-piperazine.Amine preparation: 2-Thiazolecarboxaldehyde was converted to the corresponding alcohol by treatment with sodium borohydride. Reaction with methanesulfonyl chloride yielded methanesulfonic acid thiazol-2-ylmethyl ester. A mixture of methanesulfonic acid thiazol-2-ylmethyl ester (393mg), (3R,5S)-3,5- dimethyl-piperazine-1 -carboxylic acid tert-butyl ester (described previously, 435mg), potassium carbonate (309mg) and tetrabutyl ammonium iodide (827mg) was heated to reflux in MeCN (1OmL). After 4 days the reaction mixture was cooled, diluted with ethyl acetate, washed with water and dried (MgSO4). The solvent was evaporated and the residue purified by flash chromatography to give (R)-3,5- dimethyl-4-thiazol-2-ylmethyl-piperazine-l -carboxylic acid (S) -tert-butyl ester (314mg). Treatment of this compound with HCl in DCM/MeOH yielded the desired amine, which was isolated as the hydrochloride salt. EPO <DP n="79"/>1H NMR (400MHz, CDCl3) 1.12 (d, J=6.0Hz, 6H), 2.06 (m, 2H), 2.85 (m, 4H), 3.80 (s, 2H), 3.92 (m, 4H), 4.09 (m, 4H), 4.17 (s, 2H), 7.24 (d, J=3.2Hz, IH), 7.38 (s, IH), 7.51 (m, IH), 7.59 (d, J=8.3Hz, IH), 7.74 (d, J=3.3Hz, IH), 8.29 (d, J=7.3Hz, IH), 9.03 (s, IH), 10.1 (br s, IH); MS (ESf) 561 (MH+).
		A. 1,3-Thiazol-2-ylmethanol To a solution of 1,3-thiazole-2-carbaldehyde (1.95 g, 17.3 mmol) in MeOH at rt was added NaBH4 (0.783 g, 20.7 mmol), portionwise over 5 min. The mixture was stirred 15 min, then 10% HCl was added dropwise until evolution of gas ceased. The mixture was concentrated in vacuo, the residue was partitioned between EtOAc/brine and the layers were separated. The aqueous layer was extracted with EtOAc (*2). The combined organic portions were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording 1.42 g of the title compound as a waxy yellow solid: 1H NMR (400 MHz, CDCl3) delta 7.73 (d, J=3.3 Hz, 1H), 7.32 (d, J=3.2 Hz, 1H), 4.96 (s, 2H), 3.93 (bs, 1H).
		To a suspension of aluminum lithium hydride (671 mg) in THF (20 ml), a solution of 2-thiazolecarboxyaldehyde (2.0 g) in THF (20 ml) was added dropwise at 0C under nitrogen atmosphere. After finishing the dropping, water (0.7 ml), 15% aqueous solution of sodium hydroxide (0.7 ml), and water (2.1 ml) were sequentially added to the mixture at 0C, and the mixture was stirred for 2.5 hours at room temperature. The mixture was dried over magnesium sulfate, and the insolubles were filtered off. The solvent was distilled off under reduced pressure, to give 2-hydroxymethylthiazole (1.0 g) as brown oil. 1H-NMR (200 MHz, CDCl3) delta 4.98 (2H, s), 7.33 (1H, d, J = 3.4 Hz), 7.75 (1H, d, J = 3.0 Hz)
	With methanol; sodium tetrahydroborate; In tetrahydrofuran; at 20℃; for 0.5h;	To a stirred solution of 1.00 g of 1,3-thiazole-2-carboxaldehyde in 10 mL of tetrahydrofuran was added 0.334 g of sodium borohydride at room temperature. To the mixture was dropped 1 mL of methanol, and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 0.344 g of 1,3-thiazol-2-ylmethanol.1H-NMR (CDCl3) delta ppm: 3.11 (1H, br s), 4.97 (2H, s), 7.32 (1H, d, J=3.2Hz), 7.75 (1H, d, J=3.2Hz)
	With sodium tetrahydroborate; In methanol; at 20 - 35℃; for 4h;	(i) NaBH4, eOH, 20-35C , 4h; (ii) SOCI2, DC , 20C, 0.5h; (iii) Pd(dppf)2Cl2, K2C03, DMF, 1 10C, 14h; (iv) CF3COOH, CH2C12, 20-35C, 2h; (v) Acryloyl chloride, triethylamine, CH2C12, 20-35C, 16h. (Rcf. for step-(i-ii): US2009/082403)
12 g	With sodium tetrahydroborate; In methanol; at 0 - 20℃;	To a mixture of 2-formylthiazole (84.22g, 0.75mol) and methanol (100 mL) was added sodium borohydride (120g, 1.5mol) at 0C, which was stirred for overnight at room temperature. Water was added to this reaction mixture, which was then extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography with DCM/MeOH (100:1-50:1) to afford thiazol-2-ylmethanol as light yellow oil (12 g ,14%).
230 mg	With methanol; sodium tetrahydroborate; at -60℃; for 1h;Inert atmosphere;	Step 1 thiazol-2-ylmethanol To a solution of n-BuLi (8.4 ml , 1.6 mol/1 , 13.4 mmol) in THF (30 mL) was added 2- bromothiazole (377 mg, 2.12 mmol) dropwise under nitrogen atmosphere at -70 C, and the mixture was stirred at the temperature for 1 h. Then DMF (1.4 ml, 18.3 mmol) was added into the solution dropwise under nitrogen atmosphere at -70 C. The resulting mixture was stirred at the temperature for 1 h. Then the mixture was quenched with aqueous saturated ammonium chloride, diluted with ethyl acetate and water, and the phases were separated. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give yellow oil. The yellow oil was dissolved in methanol (15 ml) , cooled to -60 C, ans sodium borohydride (463 mg , 12.2 mmol) was added portionwise under nitrogen atmosphere. The mixture was stirred at the temperature for 1 h. The reaction was quenched with acetone and concentrated. The residue was diluted with ethyl acetate and water, and the phases were separated. The organic layer was dried over sodium sulfate, filtered and concentrated, then purified by silica gel chromatography eluting with petroleum/ ethyl acetate= 3: 1 to give thiazol-2-ylmethanol (230 mg, 16.4 % yield) as brown oil . LCMS MH+ 1 16.

Reference： [1]Chinese Journal of Chemistry,2014,vol. 32,p. 538 - 544
[2]Patent: CN106749268,2017,A .Location in patent: Paragraph 0798; 0799
[3]European Journal of Organic Chemistry,2017,vol. 2017,p. 4972 - 4983
[4]Zeitschrift fur Naturforschung, B: Chemical Sciences,2007,vol. 62,p. 1525 - 1529
[5]Tetrahedron,1988,vol. 44,p. 2021 - 2032
[6]Patent: US2009/82403,2009,A1 .Location in patent: Page/Page column 147-148
[7]Patent: WO2006/21402,2006,A1 .Location in patent: Page/Page column 36
[8]Patent: WO2006/92268,2006,A1 .Location in patent: Page/Page column 22-23
[9]Patent: EP1466898,2004,A1 .Location in patent: Page 90
[10]Patent: US5512575,1996,A
[11]Patent: US2004/162285,2004,A1
[12]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4845 - 4850
[13]Patent: WO2006/19957,2006,A2 .Location in patent: Page/Page column 25
[14]Patent: US2006/116372,2006,A1 .Location in patent: Page/Page column 7
[15]Patent: US2006/116372,2006,A1 .Location in patent: Page/Page column 7
[16]Patent: WO2007/34277,2007,A1 .Location in patent: Page/Page column 55
[17]Patent: US2014/275528,2014,A1 .Location in patent: Paragraph 0304; 0305
[18]Patent: WO2014/110705,2014,A1 .Location in patent: Page/Page column 75
[19]Patent: WO2014/110687,2014,A1 .Location in patent: Page/Page column 56
[20]Journal of Organic Chemistry,1995,vol. 60,p. 4749 - 4754
[21]Journal of Materials Chemistry,1998,vol. 8,p. 833 - 835
[22]Patent: WO2006/46031,2006,A1 .Location in patent: Page/Page column 76-77
[23]Patent: US2009/170907,2009,A1 .Location in patent: Page/Page column 60
[24]Patent: EP1422228,2004,A1 .Location in patent: Page 221
[25]Patent: EP1443041,2004,A1 .Location in patent: Page 27
[26]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7414 - 7420
[27]Patent: WO2013/80222,2013,A1 .Location in patent: Page/Page column 33
[28]Patent: WO2014/66795,2014,A1 .Location in patent: Paragraph 0174 - 0175
[29]Patent: WO2014/143799,2014,A2 .Location in patent: Page/Page column 386; 387
[30]Patent: US2016/137639,2016,A1 .Location in patent: Paragraph 3410

7
[ 14527-42-5 ]
[ 14542-12-2 ]

Reference： [1]Tetrahedron,1988,vol. 44,p. 2021 - 2032

8
[ 54101-88-1 ]
[ 14542-12-2 ]

Reference： [1]Tetrahedron,1991,vol. 47,p. 2851 - 2860

Yield	Reaction Conditions	Operation in experiment
		When the following compounds are substituted for 4-hydroxymethyl-5-methylimidazole in the procedure of Example 29(i): ... 2-hydroxymethyl-3-hydroxypyridine, 2-hydroxymethyl-3-chloropyridine, 2-hydroxymethylthiazole and 3-hydroxymethylisothiazole

10
[ 50-00-0 ]
etheric thiazol-2-yl magnesium bromide [ No CAS ]
[ 14542-12-2 ]

Reference： [1]Journal of the American Chemical Society,1952,vol. 74,p. 6260

11
[ 3029-48-9 ]
natrium carbonate [ No CAS ]
[ 14542-12-2 ]

Reference： [1]Chemische Berichte,1892,vol. 25,p. 2623
Journal of the Chemical Society,1919,vol. 115,p. 1071

12
[ 3029-48-9 ]
sodium hydroxide [ No CAS ]
[ 14542-12-2 ]

Reference： [1]Chemische Berichte,1892,vol. 25,p. 2623
Journal of the Chemical Society,1919,vol. 115,p. 1071

13
[ 14542-12-2 ]
[ 4548-45-2 ]
5-nitro-2-(thiazol-2-ylmethoxy)-pyridine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 1867 - 1870

14
[ 14542-12-2 ]
[ 84424-21-5 ]
[ 475468-55-4 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5564 - 5575

15
[ 14542-12-2 ]
[ 202931-56-4 ]
3-phenyl-6-(2-thiazolyl)methyloxy-7,8,9,10-tetrahydro-(7,10-ethano)-1,2,4-triazolo[3,4-a]phthalazine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 1367 - 1383

16
[ 14542-12-2 ]
[ 1193-02-8 ]
[ 497853-74-4 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of <strong>[14542-12-2]2-hydroxymethylthiazole</strong> (660 mg) in chloroform (20 ml) was added one droplet of DMF, and thionyl chloride (0.55 ml) was added to the mixture at 0C. The mixture was allowed to be at room temperature and the mixture was stirred for 2 hours. The solvent was distilled off under reduced pressure and the obtained residue was dissolved in methanol (10 ml). This solution was added to a mixed solution of 4-aminothiophenol (600 mg) and sodium hydroxide (460 mg) in methanol (10 ml) and water (6 ml) at 0C. The mixture was allowed to be at room temperature, and stirred for 30 minutes and water was added to the mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the obtained residue was purified by basic silica gel column chromatography (hexane:ethyl acetate = 1:1), to give 4-[(thiazol-2-ylmethyl)sulfanyl]aniline (269 mg). 1H-NMR (200 MHz, CDCl3) delta 3.72 (2H, br), 4.28 (2H, s), 6.58 (2H, d, J = 8.6 Hz), 7.18 to 7.25 (3H, m), 7.65 (1H, d, J = 3.2 Hz) as colorless oil

Reference： [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 363 - 386
[2]Patent: EP1422228,2004,A1 .Location in patent: Page 221

17
[ 313679-57-1 ]
[ 14542-12-2 ]
{(1S,2R)-3-[(Benzo[1,3]dioxole-5-sulfonyl)-isobutyl-amino]-2-hydroxy-1-[4-(thiazol-2-ylmethoxy)-benzyl]-propyl}-carbamic acid (3R,3aS,6aR)-(hexahydro-furo[2,3-b]furan-3-yl) ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1788 - 1794

18
[ 14542-12-2 ]
[ 58479-61-1 ]
C₂₀H₂₃NOSSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With 1H-imidazole; In dichloromethane; for 14h;	This material (3.4 g, 29.6 mmol, 1 eq) was treated with TBDPSCI (8.94 g, 1.1 eq),imidazole (4.0 g, 2 eq) in 20 mL DCM. The mixture was stirred for 14 h. After removalof solvent, extraction with EtOAc and drying the organic layer with Na2C03,evaporation of the solvent afforded 10.5 g of the desired product quantitavely.1HNMR(CDCI35): 1.1 (s, 9 H) 4.90.(s, 2H) 7.30-7.40 (m, 7 H) 7.60-7.70

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4845 - 4850
[2]Patent: WO2006/19957,2006,A2 .Location in patent: Page/Page column 25

19
[ 14542-12-2 ]
[ 299189-75-6 ]
[ 524743-48-4 ]

Yield	Reaction Conditions	Operation in experiment
	With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; toluene; at 0 - 20℃; for 4h;	To a stirred solution of 0.454 g of <strong>[14542-12-2]1,3-thiazol-2-ylmethanol</strong>, 1.41 g of 5-cyano-2-methoxy-N-[2-(4-isopropylphenyl)ethyl]-benzenesulfonamide, and 1.55 g of triphenylphosphine in 30 mL of tetrahydrofuran was added dropwise 3.08 mL of 40 % diisopropyl diazenediyldicarboxylate - toluene solution under ice-cooling, and the mixture was stirred at room temperature for 4 hours. To the reaction mixture was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate. After the solvent was removed under reduced pressure, to the residue was added diluted hydrochloric acid to acidify, and the solvent was removed under reduced pressure. The residue was suspended with ethyl acetate, and the insoluble material was collected by filtration. After the obtained solid was suspended with ethyl acetate, to the mixture was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 0.80 g of 5-cyano-N-[2-(4-isopropylphenyl)ethyl]-2-methoxy-N-(1,3-thiazol-2-ylmethyl)benzenesulfonamide.1H-NMR (DMSO-d6) delta ppm: 1.16 (6H, d, J=6.9Hz), 2.61-2.71 (2H, m), 2.81 (1H, sept, J=6.9Hz), 3.41-3.54 (2H, m), 3.92 (3H, s), 4.87 (2H, s), 6.97 (2H, d, J=7.9Hz), 7.07 (2H, d, J=7.9Hz), 7.35 (1H, d, J=8.8Hz), 7.71 (1H, d, J=3.2Hz), 7.75 (1H, d, J=3.2Hz), 8.09 (1H, dd, J=8.8, 2.2Hz), 8.13 (1H, d, J=2.2Hz)

Reference： [1]Patent: EP1443041,2004,A1 .Location in patent: Page 27-28

20
[ 14542-12-2 ]
[ 847199-07-9 ]
[ 864262-63-5 ]

Yield	Reaction Conditions	Operation in experiment
61%	With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 20℃;	Example 16; 7-Chloro-6-(thiazol-2-ylmethoxy)-2, 3,4, 5-tetrahydro-lH-benzo [d] azepine Hydrochloride; Use a method similar to the General Procedure 4-2, using 7-chloro-6-hydroxy-3- (2,2, 2-trifluoroacetyl)-2, 3,4, 5-tetrahydro-lH-benzo [d] azepine and <strong>[14542-12-2]thiazol-2-yl-methanol</strong> (86.2 mg, 0.75 mmol) to give, after chromatography on silica gel eluting with hexane/EtOAc (9: 1 and 7: 3), 7-chloro-6- (thiazol-2-ylmethoxy)-3- (2, 2,2-trifluoroacetyl)- 2,3, 4, 5-tetrahydro-1H-benzo [d]azepine (163 mg, 61%). MS (ES+) m/z 391 (M+H) +. Use a method similar to the General Procedure 1-1 to deprotect 7-chloro-6- (thiazol-2-ylmethoxy)-3- (2, 2,2-trifluoroacetyl)-2, 3,4, 5-tetrahydro-lH-benzo [d] azepine. Purify by chromatography on silica gel eluting with DCM/2M ammonia in methanol (94: 6) to obtain the free base of the title compound (99 mg, 81 %). MS (ES+) rnlz : 295 (M+H) +. Use a method similar to the General Procedure 2-2 to give the title compound.; General Procedure 4-2; Add 7-chloro-6-hydroxy-3- (2, 2,2-trifluoroacetyl)-2, 3,4, 5-tetrahydro-lH- benzo [dJazepine (1 equiv. ), the appropriate alcohol (1. 1 equiv. ), triphenylphosphine (1. 2 equiv. ) and diethyl azodicarboxylate (1.1 equiv. ) sequentially to anhydrous THF. Stir the mixture at ambient temperature under nitrogen. Re-add triphenylphosphine (1.2 equiv. ) and diethyl azodicarboxylate (1.1 equiv. ) if the reaction is not completed (monitored by TLC). Dilute the mixture with EtOAc, wash with saturated aqueous NaHCO3, brine, dry over Na2S04 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc mixtures.

Reference： [1]Patent: WO2005/82859,2005,A1 .Location in patent: Page/Page column 59; 70-71

21
[ 14542-12-2 ]
[ 18162-48-6 ]
[ 314064-59-0 ]

Yield	Reaction Conditions	Operation in experiment
87%	With 1H-imidazole; In N,N-dimethyl-formamide;	Tert-butyldimethylsilylchloride (1.07 g, 7.1 mmol) was added as a single portion to a solution of the hydroxymethylthiazole (840 mg, 5.6 mmol) and imidazole (500 mg, 7.34 mmol) in anhydrous DMF (20 ml). The solution was stirred overnight under an argon atmosphere. Solvents were removed under vacuum and the residue was partitioned between water (100 ml) and ethyl acetate (500 ml). The organic layer was washed with brine, dried (MgSO4) and concentrated under reduced pressure. The residue was chromatographed on silica gel (200 g; eluent 5%/50%DCM/hexane) to give 2-chloro-4-t-butyldimethylsilyloxymethylthiazole (1.29 g, 4.9 mmol) in 87% yield, 1H nmr 0.11 (s, 6H), 0.94 (s, 9H), 4.78 (s, 2H), 7.08 (s, 1H).

Reference： [1]Patent: US7078403,2006,B1 .Location in patent: Page/Page column 25

22
[ 14542-12-2 ]
[ 6674-22-2 ]
[ 171268-82-9 ]

Yield	Reaction Conditions	Operation in experiment
63%	With diphenylphosphoranyl azide; In toluene;	Preparation HH1 2-azidomethyl-thiazole Diphenylphosphoryl azide (3.25 mL, 0.015 mol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (2.25 mL, 0.025 mol) were added to a solution of <strong>[14542-12-2]thiazol-2-yl-methanol</strong> (1.44 g, 0.013 mol) in toluene (20 mL) at 0 C. After 1 h the reaction was warmed to room temperature and stirred overnight. The mixture was diluted with toluene (20 mL) and washed with H2 O (3) brine (1), dried (Na2 SO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (30% ethyl acetate/hexanes) to afford the azide as a tan oil (1.1 g, 63%). IR 2098 cm. 1 H NMR (250 MHz, CDCl3) delta 7.8 (d, 1H, J=2.0 Hz); 7.4 (d, 1H, J=2.0 Hz); 4.7 (s, 2H).
63%	With diphenylphosphoranyl azide; In toluene;	2-azidomethyl thiazole Diphenylphosphoryl azide (3.25 mL, 0.015 mol) and 1,8-diazabicyclo[5.4.0] undec-7-ene (2.25 mL, 0.025 mol) were added to a solution of <strong>[14542-12-2]thiazol-2-yl-methanol</strong> (1.44 g, 0.013 mol) in toluene (20 mL) at 0 C. After 1 hour, the reaction was warmed to room temperature and stirred overnight. The mixture was diluted with toluene (20 mL) and washed with H2 O (3) brine (1), dried (Na2 SO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (30% ethyl acetate/hexanes) to afford the azide as a tan oil (1.1 g, 63%). IR: 2098 cm-1. 1 H NMR (250 MHz, CDCl3) delta7.8 (d, 1H, J=2.0 Hz); 7.4 (d, 1H, J=2.0 Hz); 4.7 (s, 2H).

Reference： [1]Patent: US5939398,1999,A
[2]Patent: US5698526,1997,A

23
[ 288-47-1 ]
5-amino-2-tolyl 2-thiazolylmethyl ether [ No CAS ]
[ 14542-12-2 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; paraformaldehyde; In diethyl ether; ethanol; hexane; chloroform; ethyl acetate;	The 5-amino-2-tolyl 2-thiazolylmethyl ether used as a starting material was obtained as follows: A solution of thiazole (5 g) in diethyl ether (50 ml) was added dropwise to n-butyl lithium (1.6M in hexane, 30 ml) which had been cooled to -70 C. and the mixture was stirred at -70 C. for 3 hours. Formaldehyde gas ?obtained by heating paraformaldehyde (5.05 g) to 140 C.! was led into the reaction mixture and the resultant mixture was allowed to warm to ambient temperature and was stirred for 16 hours. The mixture was partitioned between diethyl ether and 4M aqueous hydrochloric acid. The aqueous layer was basified by adding aqueous potassium hydroxide solution and extracted with a mixture of ethyl acetate (80 ml), chloroform (20 ml) and ethanol (20 ml). The extract was evaporated to give 2-thiazolylmethanol (.4.4 g), m.p. 46-47 C.;

Reference： [1]Patent: US5821246,1998,A

24
[ 14542-12-2 ]
[ 124-63-0 ]
[ 134514-93-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine; In dichloromethane; at 0℃; for 0.5h;	Sodium borohydride (0.17 g, 4.49 mmol) was added to a solution * of 2- thiazolecarboxaldehyde (0.39 mL, 4.44 mmol) in ethanol (25 mL). After stirring for 1.5 h at room temperature, the reaction was quenched with water and concentrated. The residue was dissolved in ethyl acetate and washed with water and brine, dried over magnesium sulfate and concentrated to give 0.27 g, (53%) of <strong>[14542-12-2]thiazol-2-yl-methanol</strong> as a tan oil which had: NMR (CDCI3) delta 7.72 (d, J = 3.3 Hz, 1 H), 7.31 (d, J = 3.3 Hz, 1 H), 4.95 9s, 2H); 2.83 (br s, 1 H). This was mixed with triethyl amine (0.33 mL, 2.37 mmol) in methylene chloride (4 mL) and cooled in ice. Methanesulfonylchloride (0.18 mL, 2.33 mmol) in methylene chloride (2mL) was added dropwise over 1 min. After 30 min stirring at O0C, the reaction was washed with water and brine, dried over magnesium sulfate and concentrated to yield 0.41 g (91 %) of methanesulfonic acid thiazol-2-ylmethyl ester as an orange oil which had: NMR (CDCI3) delta 7.83 (d, J = 3.3 Hz, 1 H), 7.45 (d, J = 3.3 Hz, 1 H), 5.50 (s, 2H), 3.06 (s, 3H).
		148 6-((3R.5SV3.5-Dimethyl-4-thiazol-2-ylmethyl-rhoirhoerazin-l-ylmethvn-2-(lH- indazol-4-yl)-4-morpholin-4- yl-thieno [3.2-d]p yrimidine.Via 2-chloro-6-((3R,5 S)-3 ,5 -dimethyl-4-thiazol-2-ylmethyl-piperazin- 1 - ylmethyl)-4-mophiholin-4-yl-thieno[3,2-d]pyrimidine, prepared from (2R,6S)-2,6- dimethyl- 1 -thiazol-2-ylmethyl-piperazine.Amine preparation: 2-Thiazolecarboxaldehyde was converted to the corresponding alcohol by treatment with sodium borohydride. Reaction with methanesulfonyl chloride yielded methanesulfonic acid thiazol-2-ylmethyl ester. A mixture of methanesulfonic acid thiazol-2-ylmethyl ester (393mg), (3R,5S)-3,5- dimethyl-piperazine-1 -carboxylic acid tert-butyl ester (described previously, 435mg), potassium carbonate (309mg) and tetrabutyl ammonium iodide (827mg) was heated to reflux in MeCN (1OmL). After 4 days the reaction mixture was cooled, diluted with ethyl acetate, washed with water and dried (MgSO4). The solvent was evaporated and the residue purified by flash chromatography to give (R)-3,5- dimethyl-4-thiazol-2-ylmethyl-piperazine-l -carboxylic acid (S) -tert-butyl ester (314mg). Treatment of this compound with HCl in DCM/MeOH yielded the desired amine, which was isolated as the hydrochloride salt. EPO <DP n="79"/>1H NMR (400MHz, CDCl3) 1.12 (d, J=6.0Hz, 6H), 2.06 (m, 2H), 2.85 (m, 4H), 3.80 (s, 2H), 3.92 (m, 4H), 4.09 (m, 4H), 4.17 (s, 2H), 7.24 (d, J=3.2Hz, IH), 7.38 (s, IH), 7.51 (m, IH), 7.59 (d, J=8.3Hz, IH), 7.74 (d, J=3.3Hz, IH), 8.29 (d, J=7.3Hz, IH), 9.03 (s, IH), 10.1 (br s, IH); MS (ESf) 561 (MH+).
	With triethylamine; In dichloromethane; at 20℃; for 0.333333h;	Example 52.1: 2-(4-{2-[4-(Thiazol-2-ylmethoxy)-phenyl]-acetyl}-piperazin-l-yl)- nicotinonitrile. To a solution of l,3-thiazole-2-yl methanol (40.0 mg, 0,347 mmol) in dichloromethane (2 mL) was added triethylamine ( 72.6 uL, 0,521 mmol) followed by methanesulfonyl chloride (59,7 mg, 0,521 mmol). The reaction mixture was stirred at room temperature for 20 minutes. The reaction mixture was quenched by the addition of aqueous saturated sodium bicarbonate and then extracted with dichloromethane (3x). The combined organic layer was washed with water, washed with brine, dried over sodium sulfate, filtered and concentrated to give the mesylate intermediate. To a mixture of 2-{4-[2-(4-hydroxy- phenyl)-acetyl]-piperazin-l-yl}-nicolinoniiotarile (40.0 mg, 0.124 mmol) in N,N- dimethylforraamide (2 mL) was added sodium hydride (60 % dispersion in oil, 8.2 mg, 0, 130 mmol). The reaction mixture was stirred for 20 minutes at room temperature under nitrogen. To the reaction mixture was then added a solution of the mesylate intermediate in N,N- dimethylfbrmamide (2 mL), The reaction mixture was stirred at 70 C for 3,5 hours, cooled to room temperature and then quenched by the addition of aqueous saturated sodium bicarbonate. The mixture was extracted with ethyl acetate (3x) and the combined organic layer was washed with water, washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel using hexanes:ethyl acetate (40:60 to 0: 100) to give 2-(4-{2-[4-(thiazol-2-ylmethoxy)-phenyl]-acetyl}-piperazin-l-yl)- nicotinonitrile (41.3 mg, 79 %) as an off-white solid. NMR (300 MHz1 CDCl3): delta(ppm) 8.69 (dd, IH), 8.59 (m, 2H), 3.35 (d, IH), 7.79 (d, 2H), 7.34 (d, 2H), 7.20 (m, IH), 6.95 (s, 2H), 6.82 (m, 2H), 5.07 (s, 2H), 3.81 (m, 4H), 3.74 (m, 2H).

With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;

Example 72: 1 -[6-(4-Methyl-piperazin- 1 -ylmethyl)-3, 4-dihydro-naphthalen-2-yl]-4- (thiazol-2-ylmethoxy)-lH-pyridin-2-one. To a solution of <strong>[14542-12-2]thiazol-2-yl-methanol</strong> (49 mg, 0.43 mmol) and Et3N (85 mg, 084 mmol) in 10 mL of anhydrous DCM at 0 C was added MsCl (64 mg, 056 mmol) dropwise. The mixture was stirred at room temperature for 1 hour. The mixture was partitioned between DCM (10 mL) and H20 (10 mL). The organic layer was separated, washed with H20 (2 x 50 mL), dried over Na2S04, and filtered. The filtrate was concentrated to give brown oil. The mixture of the brown oil, 4-hydroxy-l-[6-(4-methyl-piperazin-l-ylmethyl)- 3,4-dihydro -naphthalen-2-yl]-lH-pyridine-2-one (100 mg, 0.28 mmol) and K2C03 (117 mg, 0.84 mmol) in 10 mL of anhydrous DMF was stirred at 110 C for 16 hours. Then The mixture was filtered, and the filtrate was purified by preparative HPLC to give l-[6-(4- Methyl-piperazin- 1 -ylmethyl)-3 , 4-dihydro-naphthalen-2-yl]-4- (thiazol-2-ylmethoxy)- 1H- pyridin-2-one as a yellow solid (13.09 mg, 7% yield): 1H NMR (400 MHz, CD3OD) delta 7.84 (d, J = 3.2 Hz, 1H), 7.69 (d, J = 3.6 Hz, 1H), 7.55 (d, J = 7.6 Hz, 1H), 7.37-7.30 (m, 2H), 7.20 (d, J = 7.6 Hz, 1H), 6.58 (s, 1H), 6.29-6.28 (m, 1H), 6.10 (d, J = 2.4 Hz, 1H), 5.45 (s, 2H), 4.39 (s, 2H), 3.90-3.52 (m, 8H), 3.03-2.99 (m, 2H), 2.93 (s, 3H), 2.64-2.61 (m, 2H); ES- LCMS m/z 449 (M+H).

Reference： [1]Patent: WO2007/34277,2007,A1 .Location in patent: Page/Page column 55
[2]Patent: WO2006/46031,2006,A1 .Location in patent: Page/Page column 76-77
[3]Patent: WO2008/112440,2008,A1 .Location in patent: Page/Page column 57-58
[4]Patent: WO2013/149362,2013,A1 .Location in patent: Page/Page column 112-113

25
[ 14542-12-2 ]
[ 10486-42-7 ]
4-(chloromethyl)thiazole hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; thionyl chloride; In ethanol; chloroform; water;	EXAMPLE 12 1.1 g of 2-hydroxymethylthiazol were dissolved in 50 ml of chloroform and stirred for 2 hours at 20 with 0.82 ml of thionylchloride, and then boiled under reflux for 30 minutes. After concentration by evaporation in vacuo at 40, the residue was taken up in 20 ml of ethanol and the solution was reevaporated. A solution of 1.91 g of 1H-naphth[2,3-d]imidazole-2-thiol in 50 ml of ethanol, 2.14 g of KOH and 10 ml of water was added to the crystals of chloromethylthiazol hydrochloride obtained, and the whole was boiled for 2 hours under reflux. The solvent was removed in vacuo and the residue was worked up with ethyl acetate-water.

Reference： [1]Patent: US4182766,1980,A

26
[ 14542-12-2 ]
[ 7211-54-3 ]
[ 13623-94-4 ]
1-Nitro-2-(2-propynylamino)-2-{3-[(thiazol-2-yl)methylthio]propylamino}ethylene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In hydrogen bromide;	EXAMPLE 9 1-Nitro-2-(2-propynylamino)-2-{3-[(thiazol-2-yl)methylthio]propylamino}ethylene When 2-hydroxymethylthiazole is reacted with 3-mercaptopropylamine hydrochloride [prepared according to the procedure described in J. Org. Chem., 27, 2846 (1962)] in aqueous hydrobromic acid (48%) and the resultant amine successively treated with 1,1-bis(methylthio)-2-nitroethylene and excess propargylamine, the title compound is produced.

Reference： [1]Patent: US4200578,1980,A

27
[ 14542-12-2 ]
[ 18162-48-6 ]
2-(tert-butyldimethylsilanyloxymethyl)thiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With 1H-imidazole; In dichloromethane; at 20℃; for 0.5h;	Example 85: 2-(t°rt-Butyldimethylsilanyloxymethyl)thiazole; To a room temperature solution of thiazol-2-ylmethanol (1.00 g, 8.684 mmol) in CH2Cl2 was added imidazole (1.18 g, 17.4 mmol) followed by tert-butyldimethylsilyl chloride (1.70 g, 11.3 mmol). After 30 minutes, the mixture was quenched with 2 mL of MeOH and passed through a pad of silica gel eluting with CH2Cl2 (700 mL) and concentrated in vacuo to afford 2.01 g (100%) of the title compound.

Reference： [1]Patent: WO2008/70507,2008,A2 .Location in patent: Page/Page column 177

28
[ 14542-12-2 ]
[ 7143-01-3 ]
[ 134514-93-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 0℃; for 0.166667h;	Scheme i-3; Preparation of 13-thiaziol-2-ylmethyl methanesulfonate (i-3a); Methanesulfonic anhydride (282 mg, 1.62 mmol) and triethylamine (300 muL, 2.15 mmol) were added to a solution of l,3-thiazol-2-ylmethanol (108 mg, 0.935 mmol) in DCM (1 mL) at 0 0C. After 10 min, the reaction mixture was partitioned between EtOAc and saturated aqueous sodium bicarbonate solution. The layers were separated, and the aqueous layer washed with EtOAc. The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo to afford the title compound i-3a. mlz (ES) 194 (MH)+.

Reference： [1]Patent: WO2009/48547,2009,A1 .Location in patent: Page/Page column 40-41

29
[ 14542-12-2 ]
[ 131654-56-3 ]

Yield	Reaction Conditions	Operation in experiment
94%	With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 1h;	Following the same procedure as for E, but using <strong>[14542-12-2]2-(hydroxymethyl)-1,3-thiazole</strong> in place of Int. D and stirring at RT for 1 h, with purification on silica eluting with 10-40% EtOAc/PE, the title compound E1 was obtained in 94% yield as a pale yellow oil. The product was unstable so was used immediately in the next step. LCMS (method B): 1.84 min (178.0 and 180.0, MH+, Br isotopes)
43%	With phosphorus tribromide; In chloroform; at 25 - 85℃; for 1h;	Thiazol-2-ylmethanol (4.24 g, 36.9 mmol) was dissolved in chloroform (60 mL), and phosphorus tribromide (1.16 mL, 12.55 mmol) was added at 25 C.The temperature was raised to 85 C for 1.0 h, and cooled to 25 C.Add 10% sodium carbonate solution (50mL),Extracted with dichloromethane (50 mL × 3), washed with water (50 mL × 3),Dry anhydrous sodium sulfate (30g), concentrated,3.25 g of a brownish green oil was obtained in a yield of 43.0%.The product was taken directly to the next step without further purification.
	With N-Bromosuccinimide; triphenylphosphine; In N,N-dimethyl-formamide; at 10 - 35℃; for 1h;	Reference Example 15; 2-(bromomethyl)-1,3-thiazole 2-(Hydroxymethyl)-1,3-thiazole (337.6 mg) was dissolved in DMF (15 mL), and triphenylphosphine (923.2 mg) and NBS (626.5 mg) were added. The reaction mixture was stirred at room temperature for 1 hr, poured into saturated sodium sulfite aqueous solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and then saturated brine, dried over anhydrous magnesium sulfate and concentrated. Hexane-ethyl acetate (3:1) was added to the obtained residue, and the precipitated triphenylphosphine oxide was filtered off. The filtrate was concentrated, and the obtained residue was purified by column chromatography (hexane-ethyl acetate) to give the title compound (249.3 mg) as a brown oil.1H-NMR (CDCl3) delta: 4.77 (2H, s), 7.39 (1H, d), 7.76 (1H, d).

With carbon tetrabromide; triphenylphosphine; In diethyl ether; at 20℃; for 2h;

To a suspension of 1 ,3-thiazol-2-ylrnethanoi (1.52 g. 12.8 mmol) in Et20,carbon tetrabromide (137 mL, 14.1 mmoi) and triphenylphosphine (3.69 g, 14.1mrnol) was added at ambient temperature. The mixture was stirred for 2 h, and awhite precipitate was formed. The mixture was then filtered and the filtrate wasconcentrated under reduced pressure. The resulting residue was chromatographed(silica gel, hexane/EtOAc. 9:1 to 1:1) to afford the title compound. as a colorless liquid which was used immediately for the next reaction without further purification, m/z (ESI, -t-ve ion) 178.2 (M+H)t

Reference： [1]Inorganic Chemistry,2016,vol. 55,p. 619 - 632
[2]Dalton Transactions,2016,vol. 45,p. 7406 - 7420
[3]Patent: WO2018/130838,2018,A1 .Location in patent: Page/Page column 55
[4]Zeitschrift fur Naturforschung, B: Chemical Sciences,2007,vol. 62,p. 1525 - 1529
[5]Patent: CN104744446,2019,B .Location in patent: Paragraph 0883; 0898-0900
[6]Patent: US2009/270359,2009,A1 .Location in patent: Page/Page column 37
[7]Patent: US2016/137639,2016,A1 .Location in patent: Paragraph 3410
[8]Patent: WO2017/147410,2017,A1 .Location in patent: Page/Page column 1027; 1028

30
[ 14542-12-2 ]
[ 14752-66-0 ]
2-(4-Chlorophenylsulfonylmethyl)thiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%		Example 115: 2-(4-Chlorophenylsulfonylmethyl)thiazole To a chloroform (15 ml) solution of thiazole-2-methanol (171 mg, 1.49 mmol) was added thionyl chloride (0.33 ml, 4.47 mmol) and the resulting mixture was stirred at 50C for 11 hours.. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure.. The residue was dissolved in butanol (10 ml).. To the resulting solution were added sodium 4-chlorobenzenesulfinate (296 mg, 1.49 mmol) and potassium acetate (292 mg, 2.98 mmol).. The mixture was stirred at 70C for 24 hours.. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure.. ethyl acetate was added to the residue.. The mixture was washed successively with water and brine and then, dried over anhydrous sodium sulfate.. After filtration, the filtrate was concentrated under reduced pressure. The residue was subjected to chromatography on a silica gel column.. The fraction obtained from the hexane:ethyl acetate (=1:1) elude was concentrated under reduced pressure, whereby the title compound (169 mg, 41%) was obtained as a pale yellow solid. IR (ATR) nu: 2967, 2913, 1573, 1498, 1475, 1394, 1317, 1280, 1218, 1184, 1147, 1081, 1062, 1012, 966, 887, 825, 775, 763, 730, 700, 630, 599, 563, 549, 478, 447 cm-1.1H-NMR (400MHz, CDCl3) delta: 4.79(2H,s), 7.42(1H,d,J=3.2Hz), 7.47(2H,d,J=8.6Hz), 7.64(2H,d,J=8.8Hz), 7.72(1H,d,J=3.4Hz). MS (m/z): 274 (M++H).

Reference： [1]Patent: EP1466898,2004,A1 .Location in patent: Page 91

31
[ 14542-12-2 ]
[ 7693-46-1 ]
[ 144163-94-0 ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; In dichloromethane; at 0 - 20℃;	EXAMPLE 21; i o 1 ,3-Thiazol-2-ylmethyl 4-isopropyl- 1 ,4,6,7-tetrahydro-5H-imidazo [4,5-c] pyridine-5- carboxylate; 2-Hydroxymethylthiazole (0.97 g, 8.40 mmol) was dissolved in DCM (10 mL) at 0 0C and NMM (0.85 g, 0.81 mL, 8.40 mmol) and 4-nitrophenyl chloroformate (1.70 g, 8.40 mmol) is were added. The reaction mixture was stirred at room temperature for 5 h. A solution of Intermediate 1 (2.18 g, 4.20 mmol) and DIPEA (1.64 g, 2.21 mL, 12.7 mmol) in DCM (20 mL) was added and the resulting solution was stirred for 19 h. The solvents were removed in vacuo, the residue was dissolved in MeOH (8 mL) and 1 M aq NaOH solution (6 mL) and the reaction mixture was stirred at room temperature for 3 d and concentrated in vacuo.20 The residue was dissolved in EtOAc (100 mL) and the organic layer was washed with 1 M aq Na2CO3 solution (6 x 100 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (normal phase, 20 g, Strata SI-I, silica gigatube, DCM (200 mL) followed by 2% and 4% MeOH in DCM (200 mL each)) and reverse phase HPLC (YMC ODS-A 150 x 20 mm, 5 mum, 25 mL per min, gradient 20% to 80%25 (over 12 min) then 100% (3 min) MeOH in 10% MeOH/water) to give l,3-thiazol-2-yl- methyl 4-isopropyl-l,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carboxylate (51.8 mg, 4.0%) as a white solid.Analytical HPLC: purity 99.5% (System B, Rtau = 3.81 min); Analytical LCMS: purity 100% (System B, Rtau = 4.27 min), ES+: 307.1 [MH]+; HRMS calculated for Ci4Hi8N4O2S: so 306.1150, found 306.1153. - -

Reference： [1]Patent: WO2010/31789,2010,A1 .Location in patent: Page/Page column 42

32
[ 14542-12-2 ]
[ 96-32-2 ]
[ 878001-14-0 ]

Yield	Reaction Conditions	Operation in experiment
95%		NaH (55% dispersion in oil, 1.40 g, 33.0 mmol) was added to a stirred solution of thiazol-2-ylmethanol (3.55 g, 30.82 mmol) in THF (155 mL). The suspension was then heated to 45 0C for 1 h, and methyl bromoacetate (3.40 mL, 37.0 mmol) was added.Stirring was continued at 45 0C for 4 h. The reaction mixture was partitioned betweenEtOAc and H2O, the phases separated, and the aq. layer was extracted with EtOAc(2x). The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed in vacuo. Purification of the crude by FC (MeOH/CH2Cl2 1:9) yielded the title compound (5.50 g, 95%). LC-MS: tR = 0.62 min, ES+ = 188.14.

Reference： [1]Patent: WO2006/92268,2006,A1 .Location in patent: Page/Page column 23

33
[ 14542-12-2 ]
4-(chloromethyl)thiazole hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With thionyl chloride; In tetrahydrofuran; at 0 - 50℃;Inert atmosphere;	(E20) -(Chloromethyl)-l,3-thiazol-3-ium chlorideIn a 50 mL flask, thiazole-2-methanol (500 mg, 4.3 mmol) was dissolved in THF (2.6 mL) and cooled to 0 C under nitrogen. Thionyl chloride (377 pL, 5.2 mmol) was added dropwise and the reaction mixture was allowed to warm to room temperature then heated at 50 C for 2 h. The crude mixture was concentrated under reduced pressure to give an orange solid (684 mg, 94%).*H NMR (DMSO-c/6, 300 MHz) : delta (ppm) : 7.88-7.76 (m, 2H), 5.16-5.01 (m, 2H).

Reference： [1]Patent: WO2011/61214,2011,A1 .Location in patent: Page/Page column 67

34
[ 14542-12-2 ]
[ 883731-83-7 ]
[ 1344697-49-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4556 - 4560

35
[ 14542-12-2 ]
[ 38186-88-8 ]
[ 1351763-48-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In tetrahydrofuran; mineral oil;Inert atmosphere;	5-Fluoro-2-(thiazol-2-ylmethoxy)nicotinic acid (21s)A solution of 2-chloro-5-fluoronicotinic acid (1.69g, 9.6mmol) and thiazol-2-ylmethanol (2.65g, 23mmol) in anhydrous THF (125ml) was treated portionwise with NaH (60% dispersion in mineral oil, 1.50g, 37.5mmol) and the resulting suspension stirred overnight. The reaction mixture was diluted with water, 2M NaOH and washed with ether. The aqueous was acidified with cone. HCl and extracted into DCM. These organics were dried and reduced onto silica. Purification by column chromatography (S1O2, DCM:MeOH 1 :0?99: 1) gave the title compound.NMR delta 8.40 (1H, d, J2.8), 8.08 (1H, dd, J2.8, 8.2), 7.80 (1H, d, J3.2), 7.74 (1H, d, J 3.2), 5.69 (2H, s)

Reference： [1]Patent: WO2011/151651,2011,A1 .Location in patent: Page/Page column 71

36
[ 14542-12-2 ]
[ 1215850-29-5 ]
[ 1215850-04-6 ]

Yield	Reaction Conditions	Operation in experiment
5%		Thiazol-2-ylmethanol (64 mg, 0.56 mmol) was dissolved in 2 ml of anhydrous DMF. After adding sodium hydride (42 mg, 55 percent suspension in oil), the mixture was stirred for 30 min, [5-(6-chloropyridazin-3-yl)-3,4,5,6-tetrahydro-1H-pyrrolo[3,4-c]pyrrol-2-yl](2-trifluoromethylphenyl)methanone (100 mg, 0.25 mmol) was added, and the mixture was stirred at 150 C. for 30 h. After concentrating, water and ethyl acetate were added, and the organic phase was removed, concentrated and purified by preparative HPLC (PR18, acetonitrile/water 0.1% TFA). Yield: 6 mg (5%), M+H+: 474.01.

Reference： [1]Patent: US2012/28986,2012,A1 .Location in patent: Page/Page column 18

37
[ 14542-12-2 ]
[ 5122-82-7 ]
[ 1330778-47-6 ]

Reference： [1]ChemMedChem,2011,vol. 6,p. 1439 - 1451

38
[ 14542-12-2 ]
[ 1456807-88-7 ]
[ 1456808-46-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 20℃; for 0.333333h;	General procedure: To a solution of 28 (1mmol), PPh3 (2.5mmol) and various commercially available alcohol (2.5mmol) in dry THF (1mL) was added DEAD (2.5mmol) dropwise with intensive stirring at room temperature. 20min later, the reaction mixture was concentrated in vacuo and the corresponding intermediates 32a-v were obtained after chromatography by silica gel eluting with DCM-CH3OH. The final products 33a-v were prepared in a similar manner to the synthesis of compound 27 from 26 and characterized after purification by silica gel chromatography eluting with DCM-CH3OH.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 67,p. 39 - 53

39
[ 14542-12-2 ]
[ 98-59-9 ]
[ 1523412-31-8 ]

Reference： [1]Patent: WO2013/190510,2013,A2 .Location in patent: Page/Page column 361-362

40
[ 14542-12-2 ]
[ 1670-14-0 ]
[ 1596320-97-6 ]

Yield	Reaction Conditions	Operation in experiment
71%	With mu-diiodo-di((eta5-pentamethylcyclopentadienyl)(iodo)iridium); caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 20 - 110℃; for 20h;	General procedure: [Cp*IrI2]2 (1 mol %, 0.01 mmol), xantphos (2 mol %,0.02 mmol) and dioxane (2 mL) were stirred shortly in a Schlenk tube at room temperature. Subsequently, 3-pyridinemethanol (2.0 mmol), benzamidine hydrochloride(1.0 mmol), and cesium carbonate (1.0 mmol)were added. The mixture was heated under 110C for 20 h and then cooled down to room temperature. The resulting solution was purified by column chromatography with petroleum ether-ethyl acetate(10 : 1) as an eluent to give 2,4-diphenyl-6-(pyridin-3-yl)-1,3,5-triazine (3a) as a white solid.

Reference： [1]Organic and Biomolecular Chemistry,2014,vol. 12,p. 2761 - 2768
[2]Russian Journal of General Chemistry,2016,vol. 86,p. 380 - 386
Zh. Obshch. Khim.,2016,vol. 86,p. 380 - 386,7

41
[ 14542-12-2 ]
[ 350-30-1 ]
[ 851545-78-3 ]

Reference： [1]Chinese Journal of Chemistry,2014,vol. 32,p. 538 - 544

42
[ 14542-12-2 ]
[ 74-88-4 ]
[ 139130-53-3 ]

Yield	Reaction Conditions	Operation in experiment
96.3%		To a solution of 18b (3.18 g, 27.7 mmol) in anhydrous DMF (50 mL) was added NaH (1.44 g, 36.00 mmol). The mixture was stirred at 0C for 20 minutes. Then, the CH3I (9.410 g, 66.26 mmol) was added dropwise to the solution. The mixture was stirred at 0 C for 2 hours. EtOAc (250 mL) and water (150 mL) were added. The organic layer was separated and washed with water three times, and dried over anhydrous Na2S04. After filtration and concentration in vacuo, and the resutling residue was purified using Si02 chromatography, eluting with petroleum ether: ethyl acetate (20/1-5/1) to provide 18c (3.44 g, 96.3% yield)
96.3%		To a solution of 18b (3.18 g, 27.7 mmol) in anhydrous DMF (50 mL) was added NaH (1.44 g, 36.00 mmol). The mixture was stirred at 0C for 20 minutes. Then, the CH3I (9.410 g, 66.26 mmol) was added dropwise to the solution. The mixture was stirred at 0 C for 2 hours. EtOAc (250 mL) and water (150 mL) were added. The organic layer was separated and washed with water three times, and dried over anhydrous Na2S04. After filtration and concentration in vacuo, the residue waspurified using Si02 chromatography, eluting with petroleum ether: ethyl acetate (20/1-5/1) to provide 18c (3.44 g, 96.3% yield).
57%		Step 1: Preparation of 2-(methoxymethyl)thiazole To a solution of thiazol-2-ylmethanol (1.15 g, 10 mmol) in anhydrous N,N-dimethylformamide (10 mL) at 0 C. was added sodium hydride (60% in mineral oil, 0.52 g, 13 mmol) in portions. After the addition, the mixture was stirred at 0 C. for 20 min before iodomethane (1.49 mL, 24 mmol) was added dropwise. The reaction mixture was stirred at 0 C. for 2 h. The reaction as quenched with ethyl acetate/water (30 mL/20 mL) and extracted with ethyl acetate (20 mL*2). The combined organic phases were washed with brine (40 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (Biotage, 40 g silica, eluted with ethyl acetate in petroleum ether from 25% to 40%) to give 2-(methoxymethyl)thiazole (0.74 g, 5.74 mmol, 57%) as a colorless oil. LCMS (ESI) m/z: 130.1 [M+H]+.

Reference： [1]Patent: WO2014/110705,2014,A1 .Location in patent: Page/Page column 75
[2]Patent: WO2014/110687,2014,A1 .Location in patent: Page/Page column 56; 57
[3]Patent: US2019/330198,2019,A1 .Location in patent: Paragraph 0617

43
[ 14542-12-2 ]
[ 78137-76-5 ]
2-((4-bromo-3-nitrophenoxy)methyl)thiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With triphenylphosphine; diethylazodicarboxylate; In toluene; at 0℃;Inert atmosphere; Reflux;	To a solution of 4-bromo-3-nitrophenol (2 g, 9.17 mmol, Preparation S. 1), thiazol-2-ylmethanol (1.01 g, 9.17 mmol) and triphenylphosphine (2.9 g, 11.01 mmol) in anhydrous toluene (50 mL) was added DEAD (1.7 mL, 11.01 mmol) at about 0 °C under N2. Then the mixture was heated to reflux overnight. After cooling to rt, the mixture was concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel to give 2-((4-bromo-3-nitrophenoxy)methyl)thiazole (2 g, 69percent): ?H NMR (CDC13) 3 7.83 (d, J = 3.1 Hz, 1H), 7.63 (d, J = 8.8 Hz, 1H), 7.53 (d, J= 3.1 Hz, 1H), 7.42 (d, J= 3.1 Hz, 1H), 7.12 (dd, J= 3.1, 8.8 Hz, 1H), 5.43 (s, 2H).

Reference： [1]Patent: WO2014/210255,2014,A1 .Location in patent: Page/Page column 262; 263

44
[ 14542-12-2 ]
[ 13734-41-3 ]
C₁₄H₂₂N₂O₄S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 6 - 10

45
[ 14542-12-2 ]
tert-butyl 4-(4-(3,5-dichloro-4-hydroxyphenyl)pyridin-2-yl)piperazine-1-carboxylate [ No CAS ]
C₂₄H₂₆Cl₂N₄O₃S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 9790 - 9806

46
[ 14542-12-2 ]
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide [ No CAS ]
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-3-(thiazol-2-ylmethyl)quinazoline-6-sulfonamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 10767 - 10792

47
[ 14542-12-2 ]
4-chloro-6-((2,6-dimethylpyridin-3-yl)(hydroxy)(1-methyl-1H-1,2,3-triazol-5-yl)methyl)-2-methoxyquinolin-3-ol [ No CAS ]
C₂₅H₂₃ClN₆O₃S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 1463 - 1470

48
[ 14542-12-2 ]
3-(3-((6-fluoropyridin-3-yl)methyl)isoxazol-5-yl)pyridin-2-amine [ No CAS ]
3-(3-((6-(thiazol-2-ylmethoxy)pyridin-3-yl)methyl)isoxazol-5-yl)pyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With potassium tert-butylate; In tetrahydrofuran; for 0.5h;	To a neat mixture of 3-(3-((6-fluoropyridin-3-yl)methyl)isoxazol-5-yl)pyridin-2 -amine (Intermediate E, 50 mg, O. l9mmol) and thiazol-2-ylmethanol (2l3mg, l.85mmol) was added potassium 2-methylpropane-2-olate (1M in THF, l.85mL, l.85mmol) and the mixture was stirred for 30min. The mixture was transferred to a silica gel samplet which was subsequently loaded on to a Biotage Snap column. The residue was purified by column chromatography (Si02, hexane/ethyl acetate). Combined fractions were concentrated under reduced pressure. Residue was dissolved in acetonitrile (5mL) and water (lOmL), frozen and lyophilized to yield 3-(3-((6-(thiazol-2-ylmethoxy)pyridin-3- yl)methyl)isoxazol-5-yl)pyridin-2 -amine (36mg, 0.097mmol, 53%) as a white solid. MS: 366.1 [M+H]+.

Reference： [1]Patent: WO2019/113542,2019,A1 .Location in patent: Paragraph 0419; 0420

49
[ 14542-12-2 ]
4-[4-(6-amino-4-methoxypyridin-3-yl)piperidine-1-carbonyl]-3-fluorophenol [ No CAS ]
[ 76-05-1 ]
5-(1-{2-fluoro-4-[(1,3-thiazol-2-yl)methoxy]benzoyl}piperidin-4-yl)-4-methoxypyridin-2-amine trifluoroacetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%		4- [4-(6-Amino-4-methoxypyridin-3-yl)piperidine-l -carbonyl] -3 -fluorophenol (25.0 mg; 0.07 mmol), (l,3-thiazol-2-yl)methanol (19.6 mg; 0.17 mmol), TPP (50.0 mg; 0.19 mmol) and DTAD (40.0 mg; 0.17 mmol) in l,4-dioxane (3 mL) are stirred for 1 hour at 60C. The reaction mixture is purified by RP-HPLC (ACN/water + TFA). Yield: 31.1 mg (77%) ESI-MS: m/z = 443 [M+H]+ Rt(HPLC): 0.53 min (method 11)

Reference： [1]Patent: WO2019/161010,2019,A1 .Location in patent: Page/Page column 87

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H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 14542-12-2 ] {[proInfo.proName]}

Quality Control of [ 14542-12-2 ]

Related Doc. of [ 14542-12-2 ]

Product Details of [ 14542-12-2 ]

Calculated chemistry of [ 14542-12-2 ]

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Medicinal Chemistry

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Application In Synthesis of [ 14542-12-2 ]

[ 14542-12-2 ] Synthesis Path-Upstream 1~8

[ 14542-12-2 ] Synthesis Path-Downstream 1~49

Related Functional Groups of [ 14542-12-2 ]

Alcohols

Related Parent Nucleus of [ 14542-12-2 ]

Thiazoles

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[ 14542-12-2 ]

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[ 14542-12-2 ]