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

HRID 30162

Reaction equation

HRID 30162 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-42b3bb1e1d22421db2815608bb9ff1f2
Source dataset
uspto-grants-2008_09
Patent number
US07423053B2

Linked notes

Loading…