Acetyl chloride → N-(3-{5-[2-({(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}amino)pyrimidin-4-yl]imidazo[2,1-b][1,3]thiazol-6-yl}phenyl)acetamide

HRID 1783816Notes

Reaction equation

HRID 1783816 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]3[N:14]([C:15]=2[C:16]2[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C@@H:23]4[CH2:28][CH2:27][CH2:26][N:25]([S:29]([C:32]5[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=5)(=[O:31])=[O:30])[CH2:24]4)[N:17]=2)[CH:13]=[CH:12][S:11]3)[CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.[C:48](Cl)(=[O:50])[CH3:49]>C(Cl)Cl>[Cl:38][C:35]1[CH:34]=[CH:33][C:32]([S:29]([N:25]2[CH2:26][CH2:27][CH2:28][C@@H:23]([NH:22][C:18]3[N:17]=[C:16]([C:15]4[N:14]5[C:10]([S:11][CH:12]=[CH:13]5)=[N:9][C:8]=4[C:4]4[CH:3]=[C:2]([NH:1][C:48](=[O:50])[CH3:49])[CH:7]=[CH:6][CH:5]=4)[CH:21]=[CH:20][N:19]=3)[CH2:24]2)(=[O:31])=[O:30])=[CH:37][CH:36]=1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 574631524-[6-(3-aminophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-N-{(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}pyrimidin-2-amine

Product 1

HCID 57463069N-(3-{5-[2-({(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}amino)pyrimidin-4-yl]imidazo[2,1-b][1,3]thiazol-6-yl}phenyl)acetamideYield 90.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The 4-[6-(3-aminophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-N-{(3R)-1-[(4-chlorophenyl)-sulfonyl]piperidin-3-yl}pyrimidin-2-amine (0.1 g, 0.177 mmol) was dissolved in DCM (5 ml) and treated sequentially with Hunig's base (46 uL, 0.265 mmol) and acetyl chloride (15 uL, 0.212 mmol). The mixture was kept at room temperature for two hours then was diluted with DCM (10 ml). The organic phase was washed with water (2×10 ml) and with an aqueous sodium chloride solution (10 ml). The organic phase was dried over sodium sulfate and concentrated in vacuo, giving a yellow foam. The product was triturated in ether and filtered off, giving the title compound as a yellow solid (97 mg). M.p.=169-174° C. 400 MHz 1H NMR (DMSO-d6) δ: 9.89 (s, 1H), 8.72 (br. s, 1H), 8.12 (d, J=5.1 Hz, 1H), 7.82 (s, 1H), 7.80-7.75 (m, 2H), 7.70-7.64 (m, 3H), 7.41 (d, J=4.3 Hz, 1H), 7.37 (t, J=7.8 Hz, 1H), 7.24 (d, J=7.8 Hz, 1H), 7.13 (d, J=7.4 Hz, 1H), 6.42 (d, J=5.5 Hz, 1H), 4.00-3.90 (m, 1H), 3.74 (d, J=8.6 Hz, 1H), 3.48 (d, J=11.7 Hz, 1H), 2.54-2.43 (m, 1H), 2.34 (t, J=10.2 Hz, 1H), 2.05 (s, 3H), 1.94-1.81 (m, 2H), 1.65-1.53 (m, 1H), 1.44-1.34 (m, 1H). LCMS: 608 [M+H]. Calc. for C28H26N7O3S2Cl.0.38 water.0.41 dioxane: C, 54.68; H, 4.65; N, 15.06. Found C, 54.68; H, 4.32; N, 15.05.

Workup

  1. washThe organic phase was washed with water (2×10 ml) and with an aqueous sodium chloride solution (10 ml)
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customgiving a yellow foam
  5. customThe product was triturated in ether
  6. filtrationfiltered off

Sources & evidence

ORD record
ord-6c7e22b71814474ab8c58219646be72f
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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