Methanesulfonyl chloride → [4-Amino-2-(1-methanesulfonylpiperidin-4-ylamino)thiazol-5-yl]-(2,6-difluorophenyl)methanone

HRID 30162

반응식

HRID 30162 반응식
[NH2:1][C:2]1[N:3]=[C:4]([NH:17][CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[S:5][C:6]=1[C:7]([C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[F:16])=[O:8].[CH3:24][S:25](Cl)(=[O:27])=[O:26].C(N(CC)C(C)C)C>ClCCl>[NH2:1][C:2]1[N:3]=[C:4]([NH:17][CH:18]2[CH2:23][CH2:22][N:21]([S:25]([CH3:24])(=[O:27])=[O:26])[CH2:20][CH2:19]2)[S:5][C:6]=1[C:7]([C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[F:16])=[O:8]

참가 물질

5

반응물 3

HCID 31297Methanesulfonyl chlorideHCID 521913N,N-Diethyl-2-propanamineHCID 59789375[4-Amino-2-(piperidin-4-ylamino)thiazol-5-yl]-(2,6-difluorophenyl)methanone

생성물 1

HCID 59789374[4-Amino-2-(1-methanesulfonylpiperidin-4-ylamino)thiazol-5-yl]-(2,6-difluorophenyl)methanone

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A flask was charged with [4-amino-2-(piperidin-4-ylamino)thiazol-5-yl]-(2,6-difluorophenyl)methanone (0.25 g, crude product from step D), anhydrous dichloromethane (1.5 mL) and methanesulfonyl chloride (3 eq, 155 uL). Then Diethylisopropyl amine (6 eq, 697 uL) was added to the above mixture. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the residue was purified through a silica gel column. 0.38 g of [4-amino-2-(1-methanesulfonylpiperidin-4-ylamino)thiazol-5-yl]-(2,6-difluorophenyl)methanone was obtained as a light brown solid. The overall yield for step D and E was 15%. 1H NMR (DMSO−d6, 400 MHz): δ1.45-1.57 (m, 2H, CH2), 1.95-2.05 (m, 2H, CH2), 2.82-2.90 (m, 5H, CH3, CH2,), 3.45-3.55 (m, 2H, CH2), 3.6-4.0 (broad, 1H, CH), 7.14-7.20 (m, 2H, Aromatic), 7.45-7.55 (m, 1H, Aromatic), 8.15-8.25 (broad, 1H, NH2), 8.7-8.9 (broad, 1H, NH). HR-MS (M+H)+: Observed: 417.0865: Calculated for 417.0861. Ki for CDK1 0.003 μM; CDK2 0.005 μM; CDK4 0.006 μM.

후처리

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was purified through a silica gel column

출처 및 근거

ORD 기록
ord-42b3bb1e1d22421db2815608bb9ff1f2
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07423053B2

연결된 노트

불러오는 중…