4-Chlorobenzenesulfonyl chloride → HCID 57463190, compound

HRID 1783826Notes

Reaction equation

HRID 1783826 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][C@@H:24]4[CH2:29][CH2:28][CH2:27][NH: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.[Cl:41][C:42]1[CH:47]=[CH:46][C:45]([S:48](Cl)(=[O:50])=[O:49])=[CH:44][CH:43]=1>C(Cl)Cl>[Cl:41][C:42]1[CH:47]=[CH:46][C:45]([S:48]([N:26]2[CH2:27][CH2:28][CH2:29][C@@H: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)[CH2:25]2)(=[O:50])=[O:49])=[CH:44][CH:43]=1

Participants

5

Reactant 3

HCID 73984-Chlorobenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 57463073HCID 57463073, compound

Product 1

HCID 57463190HCID 57463190, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The 4-[6-(4-fluoro-3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-N-[(3R)-piperidin-3-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 4-chlorophenylsulfonyl chloride (0.128 g, 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, 50-75%), affording 0.281 g (94%) of the title compound as a pale yellow solid. M.p.: 142-143° C. 400 MHz 1H NMR (DMSO-d6 at 60° C.) δ: 8.71 (br. s, 1H), 8.15 (d, J=5.5 Hz, 1H), 7.80-7.74 (m, 2H), 7.70-7.64 (m, 2H), 7.42 (d, J=4.5 Hz, 1H), 7.36 (dd, J=8.6, 2.3 Hz, 1H), 7.27 (dd, J=11.3, 8.2 Hz, 1H), 7.19-7.12 (m, 2H), 6.43 (d, J=5.5 Hz, 1H), 4.00-3.90 (m, 1H), 3.84 (s, 3H), 3.77-3.70 (m, 1H), 3.52-3.44 (m, 1H), 2.56-2.42 (m, 1H), 2.34 (t, J=10.0 Hz, 1H), 1.95-1.80 (m, 2H), 1.66-1.52 (m, 1H), 1.45-1.33 (m, 1H). LCMS: 599 [M+H]. Calc. for C27H24N6O3S2FCl.0.16 water.0.74 diethyl ether: C, 53.94; H, 4.57; N, 12.60. Found C, 53.94; H, 4.19; N, 12.59.

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-f6a59214d34c4dcab59d2f49f778d980
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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