Dimethylformamide → 1-cyclopropyl-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide

HRID 1057741노트

반응식

HRID 1057741 반응식
Cl.CN(C)CCCN=C=NCC.[NH2:13][C:14]1[S:15][C:16]([S:19][CH2:20][C:21]2[O:22][C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:24][N:25]=2)=[CH:17][N:18]=1.[CH:30]1([N:33]2[CH2:38][CH2:37][CH:36]([C:39](O)=[O:40])[CH2:35][CH2:34]2)[CH2:32][CH2:31]1.CN(C)C=O>CN(C)C1C=CN=CC=1.O.C(Cl)Cl>[CH:30]1([N:33]2[CH2:34][CH2:35][CH:36]([C:39]([NH:13][C:14]3[S:15][C:16]([S:19][CH2:20][C:21]4[O:22][C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:24][N:25]=4)=[CH:17][N:18]=3)=[O:40])[CH2:37][CH2:38]2)[CH2:32][CH2:31]1

참가 물질

8

반응물 4

HCID 6228DimethylformamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 110654845-(((5-(tert-Butyl)oxazol-2-yl)methyl)thio)thiazol-2-amineHCID 162440131-CYCLOPROPylpiPERIDINE-4-CARBOXYLIC ACID

생성물 1

HCID 102023351-cyclopropyl-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide수율 65%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.0 g, 5.2 mmol, 2 eq) was added to a mixture of 2-amino-5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]thiazole (0.7 g, 2.6 mmol, 1 eq), 1-cyclopropyl-4-piperidine carboxylic acid (0.77 g, 3.9 mmol, 1.5 eq), 4-(dimethylamino)pyridine (0.16 g, 1.3 mmol, 0.5 eq), N,N-dimethylformamide (2.6 mL) and CH2Cl2 (7.8 mL). The reaction mixture was stirred at rt for 1 h, diluted with water (30 mL), and extracted with ethyl acetate (2×70 mL). The combined organic extracts were dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by flash chromatography on silica gel eluting with a gradient of 0-10% triethylamine in ethyl acetate. The material was crystallized from ethyl acetate and hexanes to provide 0.7 g (65%) of 1-cyclopropyl-N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide as white crystals. MS: 421 [M+H]+; HPLC: 100% at 3.13 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).

후처리

  1. extractionextracted with ethyl acetate (2×70 mL)
  2. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. custompurified by flash chromatography on silica gel eluting with a gradient of 0-10% triethylamine in ethyl acetate
  5. customThe material was crystallized from ethyl acetate and hexanes

출처 및 근거

ORD 기록
ord-1408a7b0c3e84d4496a848462de2ca23
출처 데이터셋
uspto-grants-2003_02
특허 번호
US06515004B1

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