Acetyl bromide → HCID 58728730, compound

HRID 1992096Notes

Reaction equation

HRID 1992096 reaction equation
[CH3:1][C:2]1[N:6]([CH:7]2[CH2:13][CH:12]3[N:14]([CH2:15][CH2:16][C:17]4([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[CH2:22][CH2:21][N:20]([C:23]([C:25]5[CH:30]=[CH:29][C:28]([S:31]([NH2:34])(=[O:33])=[O:32])=[CH:27][CH:26]=5)=[O:24])[CH2:19][CH2:18]4)[CH:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]2[CH:41]=[CH:42][CH:43]=[CH:44][C:4]=2[N:3]=1.[C:45](Br)(=[O:47])[CH3:46].C(N(CC)C(C)C)(C)C>ClCCl>[C:45]([NH:34][S:31]([C:28]1[CH:27]=[CH:26][C:25]([C:23]([N:20]2[CH2:21][CH2:22][C:17]([CH2:16][CH2:15][N:14]3[CH:12]4[CH2:11][CH2:10][CH:9]3[CH2:8][CH:7]([N:6]3[C:5]5[CH:41]=[CH:42][CH:43]=[CH:44][C:4]=5[N:3]=[C:2]3[CH3:1])[CH2:13]4)([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH2:18][CH2:19]2)=[O:24])=[CH:30][CH:29]=1)(=[O:33])=[O:32])(=[O:47])[CH3:46]

Participants

5

Reactant 3

HCID 10482Acetyl bromideHCID 81531DiisopropylethylamineHCID 9830364HCID 9830364, compound

Product 1

HCID 58728730HCID 58728730, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a precooled (0° C.) solution of 4-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]-benzene-sulfonamide (20 mg, 0.033 mmol) in dichloromethane (2 mL) was added acetyl bromide (4.2 mg, 0.034 mmol) and N,N-diisopropylethyl amine (12 μL, 0.66 mmol). The resulting mixture was stirred overnight at ambient temperature. After evaporation of the solvent, the crude product was purified by flash chromatography on silical gel, eluting with a gradient of 15-30% methanol in ethyl acetate to afford N-acetyl-4-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzene-sulfonamide as amorphous solid (14 mg, 66%). 1H NMR (300 MHz, DMSO-d6) δ 7.83 (d, J=8.1 Hz, 2H), 7.48-7.46 (m, 3H), 7.37-7.33 (m, 5H), 7.21 (br, 1H), 7.13-7.05 (m, 2H), 4.51 (t, J=8.1, 1H), 3.88 (br, 1H), 3.67-3.15 (m, 6H), 2.42 (s, 3H), 2.37-2.30 (m, 2H), 2.11-2.07 (br, 2H), 1.96-1.72 (m, 13H), 1.59 (d, J=7.4, 2H). HRMS m/z (M+H)+ calcd: 654.3114, obsd: 654.3095.

Workup

  1. customAfter evaporation of the solvent
  2. customthe crude product was purified by flash chromatography on silical gel
  3. washeluting with a gradient of 15-30% methanol in ethyl acetate

Sources & evidence

ORD record
ord-f3eb5297cf7340bba5468ce072570e6e
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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