Cyclopentanesulfonyl chloride → HCID 66547934, compound

HRID 2205956Notes

Reaction equation

HRID 2205956 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[NH:13][C:14]1[N:19]=[CH:18][C:17]2[CH:20]=[C:21]([C:23]3[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=3)[NH:22][C:16]=2[CH:15]=1)[C:5]([N:7]([CH3:9])[CH3:8])=[O:6].[CH:29]1([S:34](Cl)(=[O:36])=[O:35])[CH2:33][CH2:32][CH2:31][CH2:30]1>CN(C=O)C.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[NH:13][C:14]1[N:19]=[CH:18][C:17]2[CH:20]=[C:21]([C:23]3[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=3)[N:22]([S:34]([CH:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)(=[O:36])=[O:35])[C:16]=2[CH:15]=1)[C:5]([N:7]([CH3:9])[CH3:8])=[O:6]

Participants

6

Reactant 2

HCID 3717197Cyclopentanesulfonyl chlorideHCID 68290838HCID 68290838, compound

Product 1

HCID 66547934HCID 66547934, compoundYield 18.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

3-Chloro-N,N-dimethyl-4-(2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridin-6-ylamino)benzamide (Example 127, 25 mg, 0.063 mmol) was dissolved in dry DMF. The solution was degassed and a solution of sodium bis(trimethylsilyl)amide (0.1 ml of a 1M solution in THF, 1 mmol) was added. After 20 minutes reaction, cyclopentyl sulfonyl chloride (17 mg, 0.1 mmol) was added and the reaction heated to 60° C. for 3 hours. The reaction was cooled to room temperature and diluted with ethyl acetate and water. The organic solution was washed with brine, dried over sodium sulphate and concentrated in vacuum. The crude product was purified by silica gel column chromatography eluting with 5% methanol in ethyl acetate to afford the title compound as white foam (6 mg, 18%). 1H-NMR (500 MHz, d6-DMSO): δ 1.5 (m, 2H), 1.6 (m, 2H), 1.75 (m, 4H), 2.97 (s, 6H), 3.11 (m, 1H), 3.89 (s, 3H), 6.77 (s, 1H), 7.33 (dd, J=2 Hz, 8.6 Hz, 1H), 7.48 (d, J=2 Hz, 1H), 7.68 (s, 1H), 7.76 (s, 1H), 8.01 (s, 1H), 8.12 (d, J=8.6 Hz, 1H), 8.51 (s, 1H), 8.7 (s, 1H). ESI-HRMS Found 527.1621, calculated for C25H27ClN6O3S (M+H+): 527.1627. MPS1 IC50 (uM): 0.092

Workup

  1. customThe solution was degassed
  2. additiona solution of sodium bis(trimethylsilyl)amide (0.1 ml of a 1M solution in THF, 1 mmol) was added
  3. additionwas added
  4. temperatureThe reaction was cooled to room temperature
  5. washThe organic solution was washed with brine
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated in vacuum
  8. customThe crude product was purified by silica gel column chromatography
  9. washeluting with 5% methanol in ethyl acetate

Sources & evidence

ORD record
ord-6f4d6dd1248948e8a9fbb9bf2c594ec0
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

Loading…