Diisopropylethylamine → HCID 57433764, compound

HRID 1783829Notes

Reaction equation

HRID 1783829 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]3[N:15]([C:16]=2[C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][CH:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)[N:18]=2)[CH:14]=[CH:13][S:12]3)=[CH:5][C:4]=1[O:30][CH3:31].CCN(C(C)C)C(C)C.[CH:41]1([S:44](Cl)(=[O:46])=[O:45])[CH2:43][CH2:42]1>C(Cl)Cl>[CH:41]1([S:44]([N:27]2[CH2:26][CH2:25][CH:24]([NH:23][C:19]3[N:18]=[C:17]([C:16]4[N:15]5[C:11]([S:12][CH:13]=[CH:14]5)=[N:10][C:9]=4[C:6]4[CH:7]=[CH:8][C:3]([F:2])=[C:4]([O:30][CH3:31])[CH:5]=4)[CH:22]=[CH:21][N:20]=3)[CH2:29][CH2:28]2)(=[O:46])=[O:45])[CH2:43][CH2:42]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2760919Cyclopropanesulfonyl chlorideHCID 57433644HCID 57433644, compound

Product 1

HCID 57433764HCID 57433764, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The 4-[6-(4-fluoro-3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-N-[piperidin-4-yl]pyrimidin-2-amine hydrochloride (0.25 g, 0.50 mmol) in methylene chloride (DCM) (12 ml) was cooled to 0° C. and was treated with Hunig's base (440 μl, 2.5 mmol). The mixture was kept at 0° C. for 30 minutes then the cyclopropyl-sulfonyl chloride (72 μl, 0.60 mmol) was added. The reaction mixture was stirred at room temperature for one hour. The mixture was diluted with methylene chloride (10 ml) and was washed water (2×10 ml) and a saturated aqueous sodium chloride solution (10 ml). The organic phase was dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography using a gradient (ethyl acetate/hexanes, 30-75%), affording 0.253 g (96%) of the title compound as a pale yellow solid. M.p.: 146-148° C. 400 MHz 1H NMR (DMSO-d6 at 60° C.) δ: 8.72 (br. s, 1H), 8.13 (d, J=5.1 Hz, 1H), 7.45 (d, J=4.3 Hz, 1H), 7.35 (dd, J=8.6, 2.0 Hz, 1H), 7.26 (dd, J=11.3, 8.2 Hz, 1H), 7.25 (br. S, 1H), 7.15 (ddd, J=8.2, 4.7, 2.0 Hz, 1H), 6.41 (d, J=5.1 Hz, 1H), 3.95-3.86 (m, 1H), 3.83 (s, 3H), 3.68-3.61 (m, 2H), 3.06-2.96 (m, 2H), 2.60-2.52 (m, 1H), 2.08-1.96 (m, 2H), 1.66-1.54(m, 2H), 1.04-0.94 (m, 4H). LCMS: 529 [M+H]. Calc. for C24H25N6O3S2F.0.13 water.0.7 diethyl ether: C, 54.31; H, 5.25; N, 14.18. Found C, 54.32; H, 4.89; N, 14.19.

Workup

  1. washwas washed water (2×10 ml)
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-099ff9a3f7c245db8c7687562bf78285
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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