[ CAS No. 345627-80-7 ] {[proInfo.proName]}

Name: 345627-80-7|N-(5-(((5-(tert-Butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)piperidine-4-carboxamide|99%
Brand: Ambeed
SKU: A153280
Price: 14.0 USD
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2D 3D

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Quality Control of [ 345627-80-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 345627-80-7 ]

Product Details of [ 345627-80-7 ]

CAS No. :	345627-80-7	MDL No. :	MFCD09833875
Formula :	C₁₇H₂₄N₄O₂S₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OUSFTKFNBAZUKL-UHFFFAOYSA-N
M.W :	380.53	Pubchem ID :	3025986
Synonyms :	BMS-387032

Calculated chemistry of [ 345627-80-7 ]

Physicochemical Properties

Num. heavy atoms :	25
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.59
Num. rotatable bonds :	7
Num. H-bond acceptors :	5.0
Num. H-bond donors :	2.0
Molar Refractivity :	105.8
TPSA :	133.59 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.5 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.88
Log Po/w (XLOGP3) :	2.99
Log Po/w (WLOGP) :	2.94
Log Po/w (MLOGP) :	1.15
Log Po/w (SILICOS-IT) :	4.04
Consensus Log Po/w :	2.8

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.92
Solubility :	0.0461 mg/ml ; 0.000121 mol/l
Class :	Soluble
Log S (Ali) :	-5.46
Solubility :	0.00132 mg/ml ; 0.00000347 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-5.53
Solubility :	0.00113 mg/ml ; 0.00000298 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.96

Safety of [ 345627-80-7 ]

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

Application In Synthesis of [ 345627-80-7 ]

* 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 [ 345627-80-7 ]
Downstream synthetic route of [ 345627-80-7 ]

[ 345627-80-7 ] Synthesis Path-Upstream 1~9

1
[ 345629-23-4 ]
[ 345627-80-7 ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: With trifluoroacetic acid In dichloromethane at 30℃; for 3 h; Stage #2: With sodium hydrogencarbonate In dichloromethane	Step Ih: N-(5-((5-Tert-butyloxazol-2-yl)methylthio)thiazol-2-yl)piperidine-4- carboxamide (Compound 0110)To a mixture of compound 0109 (1.0 g, 2 mmol) in dichloromethane (20 ml) was added TFA (2 ml). The reaction mixture was stirred at 30°C for 3h. After reaction the mixture was brought to pH 7-8 with saturate NaHCO₃ and exacted with ethyl acetate. The organic phase was dried over Na₂SO₄, concentrated to give the title compound 0110 (620 mg, 82percent): mp 178.5-180°C, LCMS: 381 [M+l]⁺, ¹H NMR (CDCl₃): δ 1.164 (s, 9H), 1.720-1.795 (m, 2H), 1.923-1.969 (m, 2H), 2.714- 2.777 (m, IH), 2.889 (t, J= 12 Hz, 2H), 3.281 (s, IH), 4.046 (s, IH), 6.708 (s, IH), 7.393 (s, IH), 8.844 (m, IH).

Reference： [1] Patent: WO2009/36016, 2009, A1, . Location in patent: Page/Page column 55
[2] Journal of Medicinal Chemistry, 2004, vol. 47, # 7, p. 1719 - 1728

2
[ 76779-98-1 ]
[ 345627-80-7 ]

Reference： [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 7, p. 1719 - 1728
[2] Patent: WO2009/36016, 2009, A1,

3
[ 5469-26-1 ]
[ 345627-80-7 ]

Reference： [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 7, p. 1719 - 1728

4
[ 224441-73-0 ]
[ 345627-80-7 ]

Reference： [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 7, p. 1719 - 1728
[2] Patent: WO2009/36016, 2009, A1,

5
[ 224436-97-9 ]
[ 345627-80-7 ]

Reference： [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 7, p. 1719 - 1728
[2] Patent: WO2009/36016, 2009, A1,

6
[ 333389-44-9 ]
[ 345627-80-7 ]

Reference： [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 7, p. 1719 - 1728
[2] Patent: WO2009/36016, 2009, A1,

7
[ 498-94-2 ]
[ 345627-80-7 ]

Reference： [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 7, p. 1719 - 1728

8
[ 84358-13-4 ]
[ 345627-80-7 ]

Reference： [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 7, p. 1719 - 1728

9
[ 13547-70-1 ]
[ 345627-80-7 ]

Reference： [1] Patent: WO2009/36016, 2009, A1,

[ 345627-80-7 ] Synthesis Path-Downstream 1~64

1
[ 50-00-0 ]
[ 345627-80-7 ]
1-methyl-piperidine-4-carboxylic acid [5-(5-<i>tert</i>-butyl-oxazol-2-ylmethylsulfanyl)-thiazol-2-yl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728

2
[ 86864-60-0 ]
[ 345627-80-7 ]
[ 345629-26-7 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728

3
[ 124-63-0 ]
[ 345627-80-7 ]
1-methanesulfonyl-piperidine-4-carboxylic acid [5-(5-<i>tert</i>-butyl-oxazol-2-ylmethylsulfanyl)-thiazol-2-yl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728

4
[ 345629-23-4 ]
[ 345627-80-7 ]

Yield	Reaction Conditions	Operation in experiment
82%		Step Ih: N-(5-((5-Tert-butyloxazol-2-yl)methylthio)thiazol-2-yl)piperidine-4- carboxamide (Compound 0110)To a mixture of compound 0109 (1.0 g, 2 mmol) in dichloromethane (20 ml) was added TFA (2 ml). The reaction mixture was stirred at 30C for 3h. After reaction the mixture was brought to pH 7-8 with saturate NaHCO3 and exacted with ethyl acetate. The organic phase was dried over Na2SO4, concentrated to give the title compound 0110 (620 mg, 82%): mp 178.5-180C, LCMS: 381 [M+l]+, 1H NMR (CDCl3): delta 1.164 (s, 9H), 1.720-1.795 (m, 2H), 1.923-1.969 (m, 2H), 2.714- 2.777 (m, IH), 2.889 (t, J= 12 Hz, 2H), 3.281 (s, IH), 4.046 (s, IH), 6.708 (s, IH), 7.393 (s, IH), 8.844 (m, IH).

Reference： [1]Patent: WO2009/36016,2009,A1 .Location in patent: Page/Page column 55
[2]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728

5
[ 498-94-2 ]
[ 345627-80-7 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728

6
[ 76779-98-1 ]
[ 345627-80-7 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728
[2]Patent: WO2009/36016,2009,A1

7
[ 5469-26-1 ]
[ 345627-80-7 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728

8
[ 84358-13-4 ]
[ 345627-80-7 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728

9
1-amino-3,3-dimethylbutan-2-one hydrochloride [ No CAS ]
[ 345627-80-7 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728
[2]Patent: WO2009/36016,2009,A1

10
[ 224441-73-0 ]
[ 345627-80-7 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728
[2]Patent: WO2009/36016,2009,A1

11
[ 224436-97-9 ]
[ 345627-80-7 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728
[2]Patent: WO2009/36016,2009,A1

12
[ 333389-44-9 ]
[ 345627-80-7 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728
[2]Patent: WO2009/36016,2009,A1

13
[ 345627-80-7 ]
N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-1-(2-hydroxyethyl)-4-piperidinecarboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1719 - 1728

Yield	Reaction Conditions	Operation in experiment
		, wherein said compound of Formula I is selected from the group consisting of: N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide; (+-)-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-3-piperidinecarboxamide; (+-)-1-(2,3-dihydroxypropyl)-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide; N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-1-(1-methylethyl)-4-piperidinecarboxamide; 1-cyclopropyl-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide; N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-1-(2-hydroxyethyl)-4-piperidinecarboxamide; (R)-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-3-piperidinecarboxamide; (S)-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-3-piperidinecarboxamide; cis-4-amino-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]cyclohexylcarboxamide; and ...

15
of(+-)-1-(2,3-dihydroxypropyl)-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide [ No CAS ]
[ 107-06-2 ]
[ 56-82-6 ]
[ 345627-80-7 ]
(+/-)-1-(2,3-dihydroxypropyl)-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69 mg (59%)	With sodium tris(acetoxy)borohydride; In methanol;	EXAMPLE 3 Preparation of (+-)-1-(2,3-Dihydroxypropyl)-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide N-[5-[[[5-(1,1-Dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide (66 mg, 0.17 mmol, 1 eq) was combined with glyceraldehyde (69 mg, 0.77 mmol, 4.5 eq), sodium triacetoxyborohydride (163 mg, 0.77 mmol, 4.5 eq) and 1,2-dichloroethane (4 mL). The resulting suspension was stirred at rt for 4 h. Methanol (1 mL) was added and the reaction mixture was stirred at rt overnight, concentrated in vacuo and purified by preparative HPLC to provide 69 mg (59%) of(+-)-1-(2,3-dihydroxypropyl)-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide as a white solid. MS: 455 [M+H]+; HPLC: 100% at 3.06 min (YMC S5 ODS column 4.6*50 mm, 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm).

Reference： [1]Patent: US2002/61915,2002,A1

16
[ 1634-04-4 ]
[ 345627-80-7 ]
[ 345627-98-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	With methanesulfonic acid;	EXAMPLE 18 N-[5-[[[5-(1,1-Dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide, methanesulfonic acid salt To a slurry of N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide (100 mg, 0.26 mmol) in isopropyl alcohol (0.75 mL) was added methanesulfonic acid (0.017 mL, 0.26 mmol, 1 eq). The slurry was heated to 70 C. to give a clear solution then methyl t-butyl ether (1.5 mL) was added. Within 15 minutes a precipitate formed. The resulting mixture was stirred at 55 C. for 2 hr then at room temperature for 14 hr. The precipitate which formed was collected by filtration then dried under vacuum at 50 C. for 14 hr to afford the title compound (85%) as a colorless powder, mp 105 C. Analysis calc'd for C17H24N4O2S2.MSA.H2O: C, 43.70; H, 6.11; N, 11.32; S, 19.44. Found: C, 43.53; H, 6.14; N, 11.15; S, 19.15.
85%	With methanesulfonic acid;	EXAMPLE 18 N-[5-[[[5-(1,1-Dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide, methanesulfonic acid salt To a slurry of N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide (100 mg, 0.26 mmol) in isopropyl alcohol (0.75 mL) was added methanesulfonic acid (0.017 mL, 0.26 mmol, 1 eq). The slurry was heated to 70 C. to give a clear solution then methyl t-butyl ether (1.5 mL) was added. Within 15 minutes a precipitate formed. The resulting mixture was stirred at 55 C. for 2 hr then at room temperature for 14 hr. The precipitate which formed was collected by filtration then dried under vacuum at 50 C. for 14 hr to afford the title compound (85%) as a colorless powder, mp 105 C. Analysis calc'd for C17H24N4O2S2·MSA·H2O: C, 43.70; H, 6.11; N, 11.32; S, 19.44. Found: C, 43.53; H, 6.14; N, 11.15; S, 19.15.

Reference： [1]Patent: US6515004,2003,B1
[2]Patent: US2002/61915,2002,A1

17
2-(bromoethoxy)-t-butyldimethylsilane [ No CAS ]
[ 345627-80-7 ]
N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-1-(2-dimethyl-t-butylsilyloxyethyl)-4-piperidinecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.7g (84%)	With sodium hydrogencarbonate; triethylamine; In tetrahydrofuran; ethyl acetate; N,N-dimethyl-formamide;	A. N-[5-[[[5-(1,1-Dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]1-(2-dimethyl-t-butylsilyloxyethyl)-4-piperidinecarboxamide N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide (1.4 g, 3.68 mmol, 1 eq) was dissolved in 30 mL of N,N-dimethylformamide and 100 mL of tetrahydrofuran. 2-(Bromoethoxy)-t-butyldimethylsilane (0.79 mL, 3.68 mmol, 1 eq), and NaHCO3 were added and the reaction mixture was stirred at 50 C. for 23 h. Additional 2-(bromoethoxy)-t-butyldimethylsilane (0.9 mL) was added, and the reaction mixture was stirred at 50 C. for 22 h, cooled, concentrated in vacuo and diluted with water (25 mL). The resultant aqueous mixture was extracted with ethyl acetate (50 mL). The organic extract was dried over Na2SO4, concentrated in vacuo, and purified by flash chromatography on silica gel eluding with a gradient of 0-5% triethylamine in ethyl acetate to provide 1.7g (84%) of N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-1-(2-dimethyl-t-butylsilyloxyethyl)-4-piperidinecarboxamide as a yellow solid. MS: 539 [M+H]+; HPLC: 98% at 4.01 min (YMC S5 ODS column 4.6*50 mm, 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm).
1.7 g (84%)	With sodium hydrogencarbonate; triethylamine; In tetrahydrofuran; ethyl acetate; N,N-dimethyl-formamide;	A. N-[5-[[[5-(1,1-Dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-1-(2-dimethyl-t-butylsilyloxyethyl)-4-piperidinecarboxamide N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide (1.4 g, 3.68 mmol, 1 eq) was dissolved in 30 mL of N,N-dimethylformamide and 100 mL of tetrahydrofuran. 2-(Bromoethoxy)-t-butyldimethylsilane (0.79 mL, 3.68 mmol, 1 eq), and NaHCO3 were added and the reaction mixture was stirred at 50 C. for 23 h. Additional 2-(bromoethoxy)-t-butyldimethylsilane (0.9 mL) was added, and the reaction mixture was stirred at 50 C. for 22 h, cooled, concentrated in vacuo and diluted with water (25 mL). The resultant aqueous mixture was extracted with ethyl acetate (50 mL). The organic extract was dried over Na2SO4, concentrated in vacuo, and purified by flash chromatography on silica gel eluding with a gradient of 0-5% triethylamine in ethyl acetate to provide 1.7 g (84%) of N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-1-(2-dimethyl-t-butylsilyloxyethyl)-4-piperidinecarboxamide as a yellow solid. MS: 539 [M+H]+; HPLC: 98% at 4.01 min (YMC S5 ODS column 4.6*50 mm, 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm).

Reference： [1]Patent: US6515004,2003,B1
[2]Patent: US2002/61915,2002,A1

18
[ 89793-12-4 ]
[ 345627-80-7 ]
[ 1133000-71-1 ]

Yield	Reaction Conditions	Operation in experiment
42%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl acetamide; at 20℃; for 2h;	Step 17e: Ethyl 2-(4-(5-((5-tert-butyloxazol-2-yl)methylthio)thiazol-2- ylcarbamoyl)-piperidin- 1 -yl)pyrimidine-5-carboxylate (Compound 0606-20)To a solution of compound 0110 (380 mg, 1 mmol) and diisopropyl ethylamine (1 mL) in N, N-dimethylacetamide (3 mL) was added dropwise a solution of 0605 (3 mL). The mixture was stirred at room temperature for 2 hours, diluted with ethyl acetate and partitioned with ice water. The separated organic layer was washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate in petroleum ether 50% to 100% v/v) to give the title product 0606-20 (116 mg, 42%) as a white solid: LCMS: 531 [M+l]+, 1H NMR(DMSO-d6) delta 1.156 (s, 9H), 1.262-1.297 (m, 2H), <n="71"/>1.505-1.587 (m, 2H), 1.884-1.978 (m, 2H), 2.809-2.865 (t, J= 11.2 Hz, IH), 3.051- 3.109 (t, J= 11.6 Hz, 2H), 4.042 (s, 2H), 4.232-4.286 (q, J= 7.2, 14 Hz, 2H), 4.738- 4.771 (d, J= 13.2 Hz, 2H), 6.704 (s, IH), 7.387 (s, IH), 8.782 (s, 2H), 12.360 (s, IH).

Reference： [1]Patent: WO2009/36016,2009,A1 .Location in patent: Page/Page column 69

19
[ 89793-12-4 ]
[ 345627-80-7 ]
[ 1133000-66-4 ]

Reference： [1]Patent: WO2009/36016,2009,A1

20
[ 2969-81-5 ]
[ 345627-80-7 ]
[ 1012059-84-5 ]

Yield	Reaction Conditions	Operation in experiment
46%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	Step Ii: Ethyl 4-(4-(5-((5-tert-butyloxazol-2-yl)methylthio)thiazol-2-ylcarbamoyl) piperidin-l-yl)butanoate (Compound 0111-1)To a solution of 0110 (300 mg, 0.789 mmol) in DMF (10 ml) was added ethyl 4-bromobutanoate (153 mg, 0.789 mmol). The reaction mixture was stirred at room temperature for 30 min. K2CO3 (108 mg, 0.789 mmol) was added to the mixture and the resulting mixture was stirred at room temperature overnight. The mixture was washed with water and extracted with CH2Cl2. The organic phase was dried over Na2SO4, concentrated to give the crude product. The crude product was purified by column chromatography on silica gel (ethyl acetate/petroleum ether = 1 :1 to 100% ethyl acetate) to give the title compound 0111 (180 mg, 46%), LCMS: 496 [M+ 1]+.

Reference： [1]Patent: WO2009/36016,2009,A1 .Location in patent: Page/Page column 55

21
[ 13547-70-1 ]
[ 345627-80-7 ]

Reference： [1]Patent: WO2009/36016,2009,A1

22
[ 345627-80-7 ]
[ 1012056-30-2 ]

Reference： [1]Patent: WO2009/36016,2009,A1

23
[ 17090-28-7 ]
[ 345627-80-7 ]
1-(3-acrylamidobenzoyl)-N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)piperidine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45 mg		To a solution of 3-acrylamidobenzoic acid (70 mg, 0.36 mmol) in DMF (1 mL) was added triethyl amine (0.15 mL, 1.09 mmol), EDCI (105 mg, 0.54 mmol) and HOBt (74 mg, 0.54 mmol) and the reaction was stirred at room temperature for 15 min. To the resulting solution was added <strong>[345627-80-7]N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)piperidine-4-carboxamide</strong> (139 mg, 0.36 mmol) and the reaction was further stirred at room temperature for 18 h. The reaction mixture was poured into ice water and extracted with ethyl acetate (3 x 20 mL). The combined organic solvents were dried over Na2S04. After removal of the solvent, the residue was purified by preparative HPLC to afford the title compound (45 mg, yield 22%) as a white solid. 1H NMR (DMSO- , 400MHz): delta 12.32 (br. s, 1H), 10.28 (s, 1H), 7.76 (s, 1H), 7.69 (d, J = 8.21 Hz, 1H), 7.37-7.43 (m, 2H), 7.09 (d, J = 7.54 Hz, 1H), 6.72 (s, 1H), 6.41 (d, J = 9.98 Hz, 1H), 6.30 (d, J = 2.00 Hz, 1H), 5.76-5.81 (m, 1H), 4.46 (br. s, 1H), 4.06 (s, 2H), 3.67 (br. s, 1H), 3.06 (br. s, 1H), 2.74-2.86 (m, 2H), 1.71-1.97 (m, 2H), 1.53-1.62 (m, 2H), 1.18 (s, 9H). LCMS: [M+H]+ = 554.15; Rt = 2.68 min.

Reference： [1]Patent: WO2015/154022,2015,A1 .Location in patent: Paragraph 211; 214-215

24
[ 814-68-6 ]
[ 345627-80-7 ]
1-acryloyl-N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)piperidine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.2%	With triethylamine; In dichloromethane; at 20℃; for 16h;	<strong>[345627-80-7]N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)piperidine-4-carboxamide</strong> (13 mg, 0.0342 mmol) was dissolved in dichloromethane (0.7 mL), followed by the addition of triethylamine (0.01 mL, 0.0683 mmol) and by acryloyl chloride (6 mu, 0.0683 mmol). The reaction was stirred at room temperature for 16 h. At completion, the reaction mixture was poured into sat. NaHC03 (5 mL) and extracted with dichloromethane (5 mL x 3). Combined organics were dried over Na2S04, filtered and concentrated. The crude residue was purified by silica gel column chromatography (0-100% EtOAc/Hexanes) to afford the title compound (0.2 mg, yield 1.2%). LCMS: [M+H]+ = 435.15; Rt = 2.3 min.

Reference： [1]Patent: WO2015/154022,2015,A1 .Location in patent: Paragraph 216-217

25
[ 345627-80-7 ]
1-(3-aminobenzyl)-N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)piperidine-4-carboxamide [ No CAS ]