Methanesulfonyl chloride → HCID 86642949, compound

HRID 661931Notes

Reaction equation

HRID 661931 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:20]2[C:19]3[C:14](=[CH:15][C:16]([CH2:21][OH:22])=[CH:17][CH:18]=3)[NH:13][C:12]=2[C:11]([C:23]([NH2:25])=[O:24])=[CH:10][CH:9]=1.[CH3:26][S:27](Cl)(=[O:29])=[O:28]>C1COCC1.CCOC(C)=O>[CH3:26][S:27]([O:22][CH2:21][C:16]1[CH:17]=[CH:18][C:19]2[C:20]3[C:12](=[C:11]([C:23](=[O:24])[NH2:25])[CH:10]=[CH:9][C:8]=3[C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])[NH:13][C:14]=2[CH:15]=1)(=[O:29])=[O:28]

Participants

5

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 59375101HCID 59375101, compound

Product 1

HCID 86642949HCID 86642949, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-(2-fluorophenyl)-7-(hydroxymethyl)-9H-carbazole-1-carboxamide (Example 30-1, 223 mg, 0.667 mmol) and TEA (0.279 mL, 2.001 mmol) in THF (8 mL) was treated with methanesulfonyl chloride (0.104 mL, 1.334 mmol). The resulting suspension was stirred at rt for 15 min. The mixture was diluted with EtOAc, washed with water and brine, and dried and concentrated to provide crude (8-carbamoyl-5-(2-fluorophenyl)-9H-carbazol-2-yl)methyl methanesulfonate as a yellow glassy foam (300 mg, ca. 50% purity). A portion of this material (80 mg, 0.097 mmol) was dissolved in DMF (1 mL), treated with morpholine (84 mg, 0.970 mmol) and heated at 45° C. for 3 days. The mixture was purified by preparative HPLC to provide 4-(2-fluorophenyl)-7-(morpholinomethyl)-9H-carbazole-1-carboxamide (9.6 mg, 23%). 1H NMR (400 MHz, methanol-d4) δ 7.94 (1H, d, J=7.8 Hz), 7.59 (1H, s), 7.52-7.58 (1H, m), 7.48-7.52 (1H, m), 7.33-7.39 (1H, m), 7.30 (1H, t, J=9.0 Hz), 7.21 (1H, d, J=8.3 Hz), 7.14 (1H, d, J=7.8 Hz), 6.99 (1H, dd, J=8.3, 1.5 Hz), 3.81 (2H, s), 3.71-3.77 (4H, m), 2.66 (4H, br. s.). Mass spectrum m/z 404.2 (M+H)+.

Workup

  1. washwashed with water and brine
  2. customdried
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-b28b1f378582467b8c97ea81ecc8f850
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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