[ CAS No. 13750-63-5 ]

Name: 13750-63-5|(4-Methylthiazol-2-yl)methanol|97%
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Quality Control of [ 13750-63-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 13750-63-5 ]

Product Details of [ 13750-63-5 ]

CAS No. :	13750-63-5	MDL No. :	MFCD08236826
Formula :	C₅H₇NOS	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CQMPPPAHJBQCOY-UHFFFAOYSA-N
M.W :	129.18 g/mol	Pubchem ID :	17750909
Synonyms :

Calculated chemistry of [ 13750-63-5 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.4
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	33.21
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) :	-6.73 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.46
Log Po/w (XLOGP3) :	0.5
Log Po/w (WLOGP) :	0.79
Log Po/w (MLOGP) :	-0.47
Log Po/w (SILICOS-IT) :	2.35
Consensus Log Po/w :	0.93

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.35
Solubility :	5.74 mg/ml ; 0.0444 mol/l
Class :	Very soluble
Log S (Ali) :	-1.36
Solubility :	5.66 mg/ml ; 0.0438 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.47
Solubility :	4.35 mg/ml ; 0.0337 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.17

Safety of [ 13750-63-5 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P280-P305+P351+P338	UN#:	1760
Hazard Statements:	H318	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 13750-63-5 ]

* 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 [ 13750-63-5 ]
Downstream synthetic route of [ 13750-63-5 ]

[ 13750-63-5 ] Synthesis Path-Upstream 1~1

1
[ 13750-63-5 ]
[ 79-37-8 ]
[ 82294-70-0 ]

Reference： [1] Patent: US6277871, 2001, B1,

[ 13750-63-5 ] Synthesis Path-Downstream 1~59

1
2-benzoyloxymethyl-4-methyl-thiazole [ No CAS ]
[ 13750-63-5 ]

Reference： [1]Journal of the Chemical Society,1949,p. Spl. 113

2
[ 50-00-0 ]
[ 89602-38-0 ]
[ 13750-63-5 ]

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

3
[ 7210-73-3 ]
[ 13750-63-5 ]

Yield	Reaction Conditions	Operation in experiment
60%		Method B: Alternatively, dissolve 4-methyl-thiazole-2-carboxylic acid ethyl ester (prepare in 27% yield according to the procedures essentially as described in Erlenmeyer, H., et al., HeIv. CHm. Acta (1944), 27, 1437-1438) (1.52 g, 8.88 mmol) in THF (6OmL) and add lithium borohydride (2.0M solution in THF, 9 mL, 17.8 EPO <DP n="136"/>mmol). Heat at reflux temperature for 18 h. Allow to cool to room temperature and dilute the reaction mixture with water (20 mL). Extract into ethyl acetate (3 x 50 mL). Dry the combined organic portions (MgSO4), filter, and concentrate in vacuo at 45 0C. Purify the crude product on silica gel (40 g) with 40 - 80% EtOAc/hexanes to give 690 mg (60%) of the title compound as a colorless oil.

Reference： [1]Patent: WO2007/2181,2007,A2 .Location in patent: Page/Page column 134-145

4
[ 13750-63-5 ]
[ 506-96-7 ]
[ 59311-22-7 ]

Yield	Reaction Conditions	Operation in experiment
53%	at 0 - 20℃; for 18h;	Preparation 37; 2-Bromomethyl-5-chloro-thiopheneCool (5-chloro-thiophen-2-yl)-methanol (Preparation 30) (330 mg, 2.22 mmol) to 0 0C and add acetyl bromide (709 mg, 430 muL, 5.76 mmol). Allow to warm to room temperature over 18 h, dilute with EtOAc (10 mL), and cautiously add saturated aqueous NaHCO3 (3 mL). When the carbon dioxide evolution stops, load the mixture onto a Varian Chem Elut CE1005 solid phase extraction cartridge (Varian part number 12198006). Elute with EtOAc, collect, and concentrate about 50 mL to obtain the crude product. Purify on silica gel (12 g) using 0-15% EtOAc/hexanes to afford 250 mg (53%) of the title compound as a yellow oil. MS (EI): 210,212; 1H NMR (CDCl3): delta 6.92 (d, IH, /=3.5 Hz), 6.78 (d, IH, /=4.0 Hz), 4.66 (s, 2H).

Reference： [1]Patent: WO2007/2181,2007,A2 .Location in patent: Page/Page column 137

5
[ 13750-63-5 ]
(Z)-4-methyl-2-(3-phenyloxiranyl)thiazole [ No CAS ]

Reference： [1]Tetrahedron,2003,vol. 59,p. 1381 - 1387

6
[ 13750-63-5 ]
(E)-4-methyl-2-(3-phenyloxiranyl)thiazole [ No CAS ]

Reference： [1]Tetrahedron,2003,vol. 59,p. 1381 - 1387

7
[ 13750-63-5 ]
4-methyl-2-(1-oxaspiro[2.5]oct-2-yl)thiazole [ No CAS ]

Reference： [1]Tetrahedron,2003,vol. 59,p. 1381 - 1387

8
[ 13750-63-5 ]
(Z)-2-(1,3-diphenylaziridin-2-yl)-4-methylthiazole [ No CAS ]

Reference： [1]Tetrahedron,2003,vol. 59,p. 1381 - 1387

9
[ 13750-63-5 ]
(E)-2-(1,3-diphenylaziridin-2-yl)-4-methylthiazole [ No CAS ]

Reference： [1]Tetrahedron,2003,vol. 59,p. 1381 - 1387

10
[ 13750-63-5 ]
4-(4-methyl-thiazol-2-yl)-3-phenyl-butan-2-one [ No CAS ]

Reference： [1]Journal of the Chemical Society,1949,p. Spl. 113

11
[ 13750-63-5 ]
3-(4-methyl-thiazol-2-yl)-2-phenyl-propionitrile [ No CAS ]

Reference： [1]Journal of the Chemical Society,1949,p. Spl. 113

12
[ 68-12-2 ]
[ 13750-63-5 ]

Yield	Reaction Conditions	Operation in experiment
		Example 1: Preparation of Selected Beta-Secretase Inhibitor Compounds; Example 1.1: Synthesis of tert-butyl 3-hydroxy-4-(3-methoxybenzylammo)-l- phenylbutan-2-ylcarbamate; [0215] Methylthiazole (1.0 g, 10.1 mmol) in THF at - 78 0C was treated with n-BuLi (1.6 M, 7.56 niL) for 30 min, DMF (1.4 mL, 18.2 mmol) was added dropwise. The resulting reaction mixture was warmed to r.t. After the starting material was disappeared (by TLC), the reaction mixture was recooled to 0 0C and LAH (0.69 g, 18.5 mmol) was added. The mixture was warmed to r.t. and stirred for 1 h, the reaction was quenched with aqueous NH4Cl, diluted with EtOAc. The organic solution was separated, extracted twice with EtOAc, dried with Na2SO4, and concentrated. The residue was purified with flash chromatography to give the corresponding alcohol as a light yellow oil. 1H-NMR: (300 MHz, CDCl3), delta: 6.89 (s, 1 H); 4.95 (s, 2 H); 2.48 (s, 3 H).

Reference： [1]Patent: WO2006/110668,2006,A1 .Location in patent: Page/Page column 49

13
[ 13750-63-5 ]
[ 124-63-0 ]
[ 918792-87-7 ]

Yield	Reaction Conditions	Operation in experiment
72%	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	Preparation 34; Methanesulfonic acid 4-methyl-thiazol-2-ylmethyl esterCombine 4-methyl-thiazol-2-yl)-methanol (Preparation 30) (1.00 g, 7.74 mmol) and triethylamine (1.25 g, 1.73 mL, 12.4 mmol) in dichloromethane (30 mL) with stirring and cool to 0 0C under nitrogen. Add methanesulfonyl chloride (931 mg, 633 muL, 8.13 mmol) to the reaction mixture and stir at 0 0C for 30 min. Warm to room temperature over 30 min, then dilute with water (40 mL) and dichloromethane (40 mL). Separate the layers, dry the organic portion (MgSO4), filter, and concentrate in vacuo at 40 0C to afford 1.15 g (72%) of the title compound as a brown oil. MS (ES): m/z 208 (M+l); 1H NMR (CDCl3): delta 7.03 (m, IH), 5.48 (s, 2H), 3.11 (s, 3H), 2.50 (d, 3H, 7=0.9 Hz).
	With triethylamine; In dichloromethane; at 0℃; for 0.333333h;	Methylthiazole methanol (0.57 g, 4.4 mmol) was treated with mesyl chloride (0.42 mL, 5.4 mmol) and triethyl ethylamine at 0 0C in dichloromethane . The resulting mixture was stirred for 20 minutes followed by quenching with aqueous NH4Cl. Evaporation of the solvent from the organic layer and flash chromatography of the residue afforded the corresponding mesylate as an oil. The mesylate (0.25g, 1.2 mmol) was then dissolved in DMF and sodium azide (0.62g, 9.6 mmol) was added. The mixture was heated to reflux for 2 hours followed by cooling and washing with aqueous NH4Cl. Evaporation of the solvent from the organic layer resulted in the corresponding azide. The azide (0.14g, 0.91 mmol) was EPO <DP n="52"/>dissolved in ethyl acetate, Pd(OH)2 (0.07g) was added, and the suspension was stirred under a hydrogen atmosphere for 5 hours. The suspension was filtered through Celite. Evaporation of the solvent and flash chromatography of the residue afforded methylthiazole methylamine as a yellow oil. 1H-NMR: (300 MHz, CDCl3), delta: 6.74 (m, 1 H); 4.09 (m, 2 H); 2.37 (s, 3 H).
	With triethylamine; In dichloromethane; at 0℃; for 0.333333h;	Methylthiazole methanol (0.57 g, 4.4 mmol) was treated with mesyl chloride (0.42 mL, 5.4 mmol) and triethyl ethylamine at 0 0C in dichloromethane. The resulting mixture was stirred for 20 minutes followed by quenching with aqueous NH4Cl. Evaporation of the solvent from the organic layer and flash chromatography of the residue afforded the corresponding mesylate as an oil. The mesylate (0.25g, 1.2 mmol) was then dissolved in DMF and sodium azide (0.62g, 9.6 mmol) was added. The mixture was heated to reflux for 2 hours followed by cooling and washing with aqueous NH4Cl. Evaporation of the solvent from the organic layer resulted in the corresponding azide. The azide (0.14g, 0.91mmol) was dissolved in ethyl acetate, Pd(OH)2 (0.07g) was added, and the suspension was stirred under a hydrogen atmosphere for 5 hours. The suspension was filtered through Celite. Evaporation of the solvent and flash chromatography of the residue afforded methylthiazole methylamine as a yellow oil. 1H-NMR: (300 MHz, CDCl3), d: 6.74 (m, 1 H); 4.09 (m, 2 H); 2.37 (s, 3 H).

	With triethylamine; In dichloromethane; at 0℃; for 0.333333h;	Methylthiazole methanol (0.57 g, 4.4 mmol) was treated with mesyl chloride (0.42 mL, 5.4 mmol) and triethyl ethylamine at 0 0C in dichloromethane. The resulting mixture was stirred for 20 minutes followed by quenching with aqueous NH4Cl. Evaporation of the solvent from the organic layer and flash chromatography of the residue afforded the corresponding mesylate as an oil. The mesylate (0.25g, 1.2 mmol) was then dissolved in DMF and sodium azide (0.62g, 9.6 mmol) was added. The mixture was heated to reflux for 2 hours followed by cooling and washing with aqueous NH4Cl. Evaporation of the solvent from the organic layer resulted in the corresponding azide. The azide (0.14g, 0.91mmol) was dissolved in ethyl acetate, Pd(OH)2 (0.07g) was added, and the suspension was stirred under a hydrogen atmosphere for 5 hours. The suspension was filtered through Celite. Evaporation of the solvent and flash chromatography of the residue afforded the desired methylthiazole methylamine as a yellow oil. 1H-NMR: (300 MHz, CDCl3), d: 6.74 (m, 1 H); 4.09 (m, 2 H); 2.37 (s, 3 H).
	With triethylamine; In dichloromethane; at 0℃; for 0.333333h;	[0270] Methylthiazole methanol (0.57 g, 4.4 mmol) was treated with mesyl chloride (0.42 mL, 5.4 mmol) and triethyl ethylamine at 0 C in dichloromethane. The resulting mixture was stirred for 20 minutes followed by quenching with aqueous NH4C1. Evaporation of the solvent from the organic layer and flash chromatography of the residue afforded the corresponding mesylate as an oil. The mesylate (0.25g, 1.2 mmol) was then dissolved in DMF and sodium azide (0.62g, 9.6 mmol) was added. The mixture was heated to reflux for 2 hours followed by cooling and washing with aqueous NH4C1. Evaporation of the solvent from the organic layer resulted in the corresponding azide. The azide (0.14g, 0.91mmol) was dissolved in ethyl acetate, Pd(OH)2 (0.07g) was added, and the suspension was stirred under a hydrogen atmosphere for 5 hours. The suspension was filtered through Celite. Evaporation of the solvent and flash chromatography of the residue afforded the desired methylthiazole methylamine as a yellow oil. 1H-NMR: (300 MHz, CDC13), delta: 6.74 (m, 1 H); 4.09 (m, 2 H); 2.37 (s, 3 H).
	With triethylamine; In dichloromethane; at 0℃; for 0.333333h;	Methylthiazole methanol (0.57 g, 4.4 mmol) was treated with mesyl chloride (0.42 mL, 5.4 mmol) and triethyl ethylamine at 0 C in dichloromethane. The resulting mixture was stirred for 20 minutes followed by quenching with aqueous NH4C1. Evaporation of the solvent from the organic layer and flash chromatography of the residue afforded the corresponding mesylate as an oil. The mesylate (0.25g, 1.2 mmol) was then dissolved in DMF and sodium azide (0.62g, 9.6 mmol) was added. The mixture was heated to reflux for 2 hours followed by cooling and washing with aqueous NH4C1. Evaporation of the solvent from the organic layer resulted in the corresponding azide. The azide (0.14g, 0.91mmol) was dissolved in ethyl acetate, Pd(OH)2 (0.07g) was added, and the suspension was stirred under a hydrogen atmosphere for 5 hours. The suspension was filtered through Celite. Evaporation of the solvent and flash chromatography of the residue afforded the desired methylthiazole methylamine as a yellow oil. 1H-NMR: (300 MHz, CDC13), delta: 6.74 (m, 1 H); 4.09 (m, 2 H); 2.37 (s, 3 H).
	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	III. Methanesulfonic acid 4-methyl-thiazol-2-ylmethyl ester To a stirred solution of <strong>[13750-63-5](4-methyl-thiazol-2-yl)-methanol</strong> (1.5 g, 11.6 mmol) and Et3N (4.85 mL, 34.8 mmol) in DCM (50 mL) was added MsCl (2.7 mL, 34.8 mmol) in dropwise at 0C. After the additional, the mixture was stirred for 1 hour at room temperature. The reaction mixture was quenched by water (15 mL), extracted with ethyl acetate (3 x 20 mL). The combined organic phase was dried over Na2S04, filtered and concentrated in vacuum to give the crude product methanesulfonic acid 4-methyl-thiazol-2- ylmethyl ester (2.4 g, 100% yield): lR NMR (400 MHz, CDC13) delta 7.01 (s, 1H), 5.43 (s, 2H), 3.13 (s, 3H), 2.46 (s, 3H).

Reference： [1]Patent: WO2007/2181,2007,A2 .Location in patent: Page/Page column 136
[2]Patent: WO2006/110668,2006,A1 .Location in patent: Page/Page column 49-50
[3]Patent: WO2009/15369,2009,A2 .Location in patent: Page/Page column 75
[4]Patent: WO2009/42694,2009,A1 .Location in patent: Page/Page column 65
[5]Patent: WO2011/130383,2011,A1 .Location in patent: Page/Page column 79
[6]Patent: WO2012/54510,2012,A1 .Location in patent: Page/Page column 81-82
[7]Patent: WO2013/149362,2013,A1 .Location in patent: Page/Page column 34-35
[8]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 668 - 672

14
[ 13750-63-5 ]
[ 156-57-0 ]
[ 55904-83-1 ]
3-methoxy-4-{2-[(4-methylthiazol-2-yl)methylthio]ethylamino}-1,2,5-thiadiazole 1,1-dioxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride;	EXAMPLE 39 When 2-chloromethyl-4-methyltriazole [prepared by the reaction of thionyl chloride and 2-hydroxymethyl-4-methylthiazole, which itself is prepared according to the procedure of J. Chem. Soc., (Suppl. Issue No. 1), S106-111 (1966) or Acta Chem. Scand., 20, 2649 (1966)] is reacted with cysteamine hydrochloride and about two equivalents of a strong base such as sodium methoxide, and the resultant amine is treated with 3,4-dimethoxy-1,2,5-thiadiazole 1,1-dioxide, there is produced 3-methoxy-4-{2-[(4-methylthiazol-2-yl)methylthio]ethylamino}-1,2,5-thiadiazole 1,1-dioxide.
	With thionyl chloride;	EXAMPLE 39 When 2-chloromethyl-4-methylthiazole [prepared by the reaction of thionyl chloride and 2-hydroxymethyl-4-methylthiazole, which itself is prepared according to the procedure of J. Chem. Soc., (Suppl. Issue No. 1), S106-111 (1966) or Acta Chem. Scand., 20, 2649 (1966)] is reacted with cysteamine hydrochloride and about two equivalents of a strong base such as sodium methoxide, and the resultant amine is treated with 3,4-dimethoxy-1,2,5-thiadiazole 1,1-dioxide, there is produced 3-methoxy-4-{2-[(4-methylthiazol-2-yl)methylthio]ethylamino}-1,2,5-thiadiazole 1,1-dioxide.

Reference： [1]Patent: US4471122,1984,A
[2]Patent: US4510309,1985,A

15
[ 13750-63-5 ]
[ 156-57-0 ]
[ 13623-94-4 ]
1-nitro-2-methylthio-2-{2-[(4-methylthiazol-2-yl)methylthio]ethylamino}ethylene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride;	EXAMPLE 15 When 2-chloromethyl-4-methylthiazole [prepared by the reaction of thionyl chloride and 2-hydroxymethyl-4-methylthiazole, which itself is prepared according to the procedure of J. Chem. Soc., (Suppl. Issue No. 1), S106-111 (1966) or Acta Chem. Scand., 20, 2649 (1966)] is reacted with cysteamine hydrochloride and about two equivalents of a strong base such as sodium methoxide, and the resultant amine is treated with 1,1-bis(methylthio)-2-nitroethylene, there is produced 1-nitro-2-methylthio-2-{2-[(4-methylthiazol-2-yl)methylthio]ethylamino}ethylene.

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

16
[ 50398-72-6 ]
[ 13750-63-5 ]
[ 156-57-0 ]
[ 10191-60-3 ]
N-cyano-N'-{2-[(4-methylthiazol-2-yl)methylthio]ethyl}-S-methylisothiourea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride;	EXAMPLE 16 When 2-chloromethyl-4-methylthiazole [prepared from 2-hydroxymethyl-4-methylthiazole and thionyl chloride] is reacted with cysteamine hydrochloride and about two equivalents of a strong base such as sodium methoxide and the resultant amine treated with dimethyl cyanodithioimidocarbonate there is produced N-cyano-N'-{2-[(4-methylthiazol-2-yl)methylthio]ethyl}-S-methylisothiourea.

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

17
[ 13750-63-5 ]
[ 79-37-8 ]
[ 82294-70-0 ]

Yield	Reaction Conditions	Operation in experiment
461.0 mg (87%)	In dichloromethane; dimethyl sulfoxide;	EXAMPLE 22D 4-methylthiazole-5-carboxaldehyde A 3-neck, 100 mL round-bottom flask was charged with anhydrous CH2Cl2 (15 mL) and oxalyl chloride (0.54 mL, 6.24 mmol) under N2 atmosphere. The mixture was cooled to -78 C. Anhydrous DMSO (0.59 mL, 8.32 mmol) was slowly added. The reaction was allowed to stir for 30 minutes. The product from Example 22C (537.5 mg, 4.16 mmol) in CH2Cl2 (5 mL) was slowly added. The reaction was allowed to stir for approximately 3 hours, until TLC (1:1 EtOAc/hexanes) showed no starting material. The reaction was quenched with triethylamine (2.4 mL, 16.64 mmol) and stirred for 10 minutes before warming to room temperature. The reaction was poured into Et2O (100 mL) and extracted with water (2*25 mL). The organic phase was washed with NaHCO3 (25 mL) and brine. The organic phase was dried (MgSO4) and concentrated under vacuum. The crude product was stored in the freezer to provide 461.0 mg (87%) of the title compound as an orange crystalline solid. 1H NMR (300 MHz, CDCl3) delta 10.15, s, 1H; 8.9, s, 1H; 2.8, s, 3H.

Reference： [1]Patent: US6277871,2001,B1

18
[ 693-95-8 ]
[ 68-12-2 ]
[ 13750-63-5 ]

Yield	Reaction Conditions	Operation in experiment
		Example 1Synthesis of Heterocycle AlcoholsExample 1.1; Methylthiazole Methanol Methylthiazole (1.0 g, 10.1 mmol) in THF at -78 C. was treated with n-BuLi (1.6 M, 7.56 mL) for 30 min, DMF (1.4 mL, 18.2 mmol) was added dropwise. The resulting reaction mixture was warmed to r.t. After the starting material was disappeared (by TLC), the reaction mixture was recooled to 0 C. and LAH (0.69 g, 18.5 mmol) was added. The mixture was warmed to r.t. and stirred for 1 h, the reaction was quenched with aqeuous NH4Cl, diluted with EtOAc. The organic solution was separated, extracted twice with EtOAc, dried with Na2SO4, and concentrated. The residue was purified with flash chromatography to give the corresponding alcohol as a light yellow oil. 1H-NMR: (300 MHz, CDCl3), delta: 6.89 (s, 1H); 4.95 (s, 2H); 2.48 (s, 3H).
		Example 1.1: Synthesis of Amine Building Blocks.; Example 1.1.1: (4-methylthiazol-2-yl)methanamine; Methylthiazole (1.0 g, 10.1 mmol) in THF at - 78 0C was treated with n-BuLi (1.6 M, 7.56 mL) for 30 min, DMF (1.4 rnL, 18.2 mmol) was added dropwise. The resulting reaction mixture was warmed to r.t. After the starting material disappeared (by TLC), the reaction mixture was recooled to 0 0C and LAH (0.69 g, 18.5 mmol) was added. The mixture was warmed to r.t. and stirred for 1 h, the reaction was quenched with aqueous NH4Cl, diluted with EtOAc. The organic solution was separated, extracted twice with EtOAc, dried with Na2SO4, and concentrated. The residue was purified with flash chromatography to give the corresponding alcohol as a light yellow oil. 1H-NMR: (300 MHz, CDCl3), d: 6.89 (s, 1 H); 4.95 (s, 2 H); 2.48 (s, 3 H).
		[0269] Methylthiazole (1.0 g, 10.1 mmol) in THF at - 78 C was treated with n-BuLi (1.6 M, 7.56 mL) for 30 min, DMF (1.4 mL, 18.2 mmol) was added dropwise. The resulting reaction mixture was warmed to r.t. After the starting material disappeared (by TLC), the reaction mixture was recooled to 0 C and LAH (0.69 g, 18.5 mmol) was added. The mixture was warmed to r.t. and stirred for 1 h, the reaction was quenched with aqueous NH4C1, diluted with EtOAc. The organic solution was separated, extracted twice with EtOAc, dried with Na2S04, and concentrated. The residue was purified with flash chromatography to give the corresponding alcohol as a light yellow oil. 1H-NMR: (300 MHz, CDC13), delta: 6.89 (s, 1 H); 4.95 (s, 2 H); 2.48 (s, 3 H).

Methylthiazole (1.0 g, 10.1 mmol) in tetrahydrofuran (THF) at - 78 C was treated with n-BuLi (1.6 M, 7.56 mL) for 30 min, dimethylformamide (DMF) (1.4 mL, 18.2 mmol) was added dropwise. The resulting reaction mixture was warmed to r.t. After the starting material disappeared (by TLC), the reaction mixture was recooled to 0 C and lithium aluminum hydride (LAH) (0.69 g, 18.5 mmol) was added. The mixture was warmed to r.t. and stirred for 1 h, the reaction was quenched with aqueous NH4C1, diluted with ethyl acetate (EtOAc). The organic solution was separated, extracted twice with EtOAc, dried with Na2S04, and concentrated. The residue was purified with flash chromatography to give the corresponding alcohol as a light yellow oil. 1H-NMR: (300 MHz, CDC13), delta: 6.89 (s, 1 H); 4.95 (s, 2 H); 2.48 (s, 3 H).

Reference： [1]Patent: US2008/125467,2008,A1 .Location in patent: Page/Page column 19
[2]Patent: WO2009/42694,2009,A1 .Location in patent: Page/Page column 64-65
[3]Patent: WO2011/130383,2011,A1 .Location in patent: Page/Page column 79
[4]Patent: WO2012/54510,2012,A1 .Location in patent: Page/Page column 81

19
[ 13750-63-5 ]
[ 74124-79-1 ]
[ 881009-02-5 ]

Yield	Reaction Conditions	Operation in experiment
97%	With triethylamine; In acetonitrile; at 20℃; for 15h;	Example 2.8Synthesis of Heterocycle Mixed Carbonate; To a stirred solution of 4-methyl thiazole methanol (0.47 g, 3.6 mmol) in CH3CN (15 mL) was added triethylamine (1.5 mL, 11 mmol) and N,N'-disuccinnimidyl carbonate (1.12 g, 4.4 mmol). The resulting mixture was stirred at room temperature for 15 h and was concentrated under reduced pressure. The residue was dissolved in EtOAc and saturated NaHCO3. The layers were separated and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layer was washed with brine, dried with Na2SO4 and concentrated under reduced pressure to provide mixed carbonate 8e (955 mg, 97%) which was used for next step without further purification.

Reference： [1]Patent: US2008/125467,2008,A1 .Location in patent: Page/Page column 24

20
[ 693-95-8 ]
[ 13750-63-5 ]

Yield	Reaction Conditions	Operation in experiment
		Example 1.1: Synthesis of Amine Building Blocks.; Example 1.1.1: (4-methylthiazol-2-yl)methanamine; Methylthiazole (1.0 g, 10.1 mmol) in THF at - 78 0C was treated with n-BuLi (1.6 M, 7.56 mL) for 30 min, DMF (1.4 rnL, 18.2 mmol) was added dropwise. The resulting reaction mixture was warmed to r.t. After the starting material disappeared (by TLC), the reaction mixture was recooled to 0 0C and LAH (0.69 g, 18.5 mmol) was added. The mixture was warmed to r.t. and stirred for 1 h, the reaction was quenched with aqueous NH4Cl, diluted with EtOAc. The organic solution was separated, extracted twice with EtOAc, dried with Na2SO4, and concentrated. The residue was purified with flash chromatography to give the corresponding alcohol as a light yellow oil. 1H-NMR: (300 MHz, CDCl3), d: 6.89 (s, 1 H); 4.95 (s, 2 H); 2.48 (s, 3 H).

Reference： [1]Patent: WO2009/15369,2009,A2 .Location in patent: Page/Page column 75

21
[ 13750-63-5 ]
[ 1137879-81-2 ]

Yield	Reaction Conditions	Operation in experiment
	With diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene; In toluene;Product distribution / selectivity;	Diphenylphosphoryl azide (DPPA) (1.2 eq) and l,8-Diazabicyclo(5.4.0)undec-7-ene (DBU) (1.2 eq) were added to a stirred solution of <strong>[13750-63-5](4-methylthiazol-2-yl)methanol</strong> (1 eq) in 7 ml anh. toluene under Ar. After stirring overnight, the solvent was removed in vacuo. Purification via flash chromatography yielded2-(azidomethyl)-4-methylthiazole.
	With diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene; In toluene;Inert atmosphere;	0272] Diphenylphosphoryl azide (DPPA) (1.2 eq) and l,8-Diazabicyclo(5.4.0)undec-7-ene (DBU) (1.2 eq) were added to a stirred solution of <strong>[13750-63-5](4-methylthiazol-2-yl)methanol</strong> (1 eq) in 7 ml anh. toluene under Ar. After stirring overnight, the solvent was removed in vacuo.Purification via flash chromatography yielded2-(azidomethyl)-4-methylthiazole.
	With diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene; In toluene;Inert atmosphere;	Diphenylphosphoryl azide (DPPA) (1.2 eq) and l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (1.2 eq) were added to a stirred solution of <strong>[13750-63-5](4-methylthiazol-2-yl)methanol</strong> (1 eq) in 7 ml anh. toluene under Ar. After stirring overnight, the solvent was removed in vacuo.Purification via flash chromatography yielded2-(azidomethyl)-4-methylthiazole.

Reference： [1]Patent: WO2009/42694,2009,A1 .Location in patent: Page/Page column 65
[2]Patent: WO2011/130383,2011,A1 .Location in patent: Page/Page column 80
[3]Patent: WO2011/130383,2011,A1
[4]Patent: WO2012/54510,2012,A1
[5]Patent: WO2012/54510,2012,A1 .Location in patent: Page/Page column 82

22
[ 13750-63-5 ]
[ 1173897-87-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 50℃;	PREPARATION 115(5-Bromo-4-methyl-thiazol-2-yl)-methanolTo a solution of 4-methyl-thiazole (10 g, 100 mmol) in dry THF (300 mL) was added n- BuLi in hexane (60 mL, 150 mmol, 2.5 M) dropwise at -70C, and the mixture was stirred at -70C for 1.5 hour, DMF (12 mL) was added to the slurry over 15 min, and the mixture was stirred at -70C for 3 hours. TLC (petroleum etherEtOAc 10:1 ) indicated the reaction was completed. The mixture was warmed to 0C, and poured onto wet-ice. The mixture was acidified by 2N HCI to pH ~ 4, and extracted with EtOAc (100 mL chi 3). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate, and concentrated in vacuum to give 4-methyl-thiazole-2-carbaldhyde (10 g, 78.7%) as brown oil.To a solution of 4-methyl-thiazole-2-carbaldhyde (10.0 g, 78 mmol) in dry THF (80 mL) was added NaBH4 (1.49 g, 39 mmol), and the mixture was stirred at room temperature for 2 hours. TLC (petroleum etherEtOAc 2:1 ) indicated the reaction was completed. The mixture was diluted with NH4CI solution (50 mL) and the mixture was filtered. The filtrate was extracted with EtOAc (50 mL chi 3). The combined organic layers were washed with brine (50 mL), dried over sodium sulfate, and concentrated in vacuum to give the residue which was purified by a silica gel column eluting with petroleum etherEtOAc 3:1 to give (4-Methyl-thiazol-2-yl)-methanol (7 g, 70%) as a yellow oil.To a solution of <strong>[13750-63-5](4-methyl-thiazol-2-yl)-methanol</strong> (7.0 g, 54.3 mmol) in DMF (80 mL) was added NBS (10.6 mg, 59.6 mmol), and the mixture was stirred at 50C overnight. TLC (petroleum etherEtOAc 2:1 ) indicated the reaction was completed. The mixture was diluted with H20 (50 mL) and extracted with EtOAc (50 mL chi 3). The combined organic layers were washed with brine (50 mL 3), dried over sodium sulfate, and concentrated in vacuum to give the residue which was purified by a silica gel column (petroleum etherEtOAc 10:1 ) to give the title compound (1 1.2 g, 99%) as a brown solid.
78%	With N-Bromosuccinimide; In acetonitrile; at 20℃; for 2h;	To a solution of 29 (10.0 g, 77 mmol) in MeCN (387 mL) was added NBS (13.8 g, 77.0 mmol) at room temperature. After being stirred for 2 h at room temperature, the reaction mixture was concentrated in vacuo. The residue was diluted with EtOAc, washed with saturated aqueous NH4Cl solution, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 33% EtOAc in hexane) to give 12.6 g (78%) of 30 as yellow solid. 1H NMR (400 MHz, CDCl3)d 2.37 (3H, s), 2.74 (1H, brs), 4.85 (2H, s).
75%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 50℃; for 2h;	To a solution of thiazole 21a (720 mg, 5.58 mmol) in DMF (15 mL) was added NBS (1.1 g, 6.14 mmol) and the mixture was stirred at 50C for 2 hours. After the completion of the reaction, the mixture was diluted with water and was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to give a residue which was purified in ISCO max gradient 40% EtOAc/hexane to give the pure product (870 mg, 75% yield). 1H NMR (CDCl3, 400 MHz) 8: 4.83 (s, 2H), 4.01 (bs, 1H), 2.36 (s, 3H).

With N-Bromosuccinimide; In N,N-dimethyl-formamide;Reflux;

To a solution of Intermediate 53 (252 mg) in DMF was added N-bromosuccinimide (385 mg). The mixture was heated under reflux overnight. The solvent was evaporated under vacuum and the residue obtained was purified by column chromatography on silica gel using hexane/EtOAc as eluent to give 95 mg of the title compound as a brown solid. 1H-NMR (delta, ppm, CDCl3): 4.86 (s, 2H), 2.38 (s, 3H).

Reference： [1]Patent: WO2011/138751,2011,A2 .Location in patent: Page/Page column 119-120
[2]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3098 - 3115
[3]Patent: WO2013/142712,2013,A1 .Location in patent: Page/Page column 49
[4]Patent: EP2080761,2009,A1 .Location in patent: Page/Page column 38

23
[ 13750-63-5 ]
[ 51221-45-5 ]

Reference： [1]Patent: WO2011/130383,2011,A1
[2]Patent: WO2011/130383,2011,A1
[3]Patent: WO2012/54510,2012,A1
[4]Patent: WO2012/54510,2012,A1

24
[ 13750-63-5 ]
[ 5122-82-7 ]
[ 1330778-48-7 ]