Acetyl chloride → HCID 178474840, compound

HRID 1993896Notes

Reaction equation

HRID 1993896 reaction equation
[Cl:1][C:2]1[CH:33]=[CH:32][C:5]2[N:6]([C@@H:13]3[CH2:18][CH2:17][C@H:16]([NH:19][CH2:20][C@@H:21]4[CH2:29][C:28]5[C:23](=[CH:24][CH:25]=[C:26]([C:30]#[N:31])[CH:27]=5)[CH2:22]4)[CH2:15][CH2:14]3)[C:7]([C:9]([OH:12])([CH3:11])[CH3:10])=[N:8][C:4]=2[CH:3]=1.C(N(CC)CC)C.[C:41](Cl)(=[O:43])[CH3:42]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[CH:33]=[CH:32][C:5]2[N:6]([C@@H:13]3[CH2:14][CH2:15][C@H:16]([N:19]([CH2:20][C@@H:21]4[CH2:29][C:28]5[C:23](=[CH:24][CH:25]=[C:26]([C:30]#[N:31])[CH:27]=5)[CH2:22]4)[C:41](=[O:43])[CH3:42])[CH2:17][CH2:18]3)[C:7]([C:9]([OH:12])([CH3:11])[CH3:10])=[N:8][C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 178458923HCID 178458923, compound

Product 1

HCID 178474840HCID 178474840, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of cis-(S)-2-({4-[5-chloro-2-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-cyclohexylamino}-methyl)-indan-5-carbonitrile (25 mg, 0.054 mmol) in methylene chloride (5 mL) was added triethylamine (11 mg, 0.108 mmol), acetyl chloride (5 mg, 0.063 mmol) and trace amount of 4-dimethylaminopyridine. The mixture was stirred at room temperature for 65 hours. The reaction mixture was diluted with dichloromethane and the solution was washed with saturated aqueous sodium bicarbonate solution followed by brine. The organic extract was dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was subjected to column chromatography, eluting with dichloromethane and ethyl acetate in the presence of 4% methanol to give cis-(S)—N-{4-[5-chloro-2-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-cyclohexyl}-N-(5-cyano-indan-2-ylmethyl)-acetamide (15 mg). LC-MS showed a single peak, C29H33ClN4O2 (m/e) calcd 504.2292, obsd 505.3. 1H-NMR (CD3OD) □ 7.67 (br, 1H) 7.59 (s, 2H), 7.50 (d, 1H), 7.40 (d, 1H), 7.23 (d, 1H), 5.57 (m, 1H), 3.48 (br d, 2H), 3.15 (m, 2H), 2.97 (m, 1H), 2.84 (m, 2H), 2.59 (br, 2H), 2.32 (br, 1H), 2.11 (br s, 2H), 1.93 (m, 4H), 1.72 (s, 6H), 1.28 (s, 3H).

Workup

  1. washthe solution was washed with saturated aqueous sodium bicarbonate solution
  2. extractionThe organic extract
  3. dry with materialwas dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. washeluting with dichloromethane and ethyl acetate in the presence of 4% methanol

Sources & evidence

ORD record
ord-da8bac7dd6fa4b2ca592bf36c4e83bb5
Source dataset
uspto-grants-2010_01
Patent number
US07652053B2

Reaction notes

Loading…