Acetyl chloride → HCID 66588054, compound

HRID 1408171Notes

Reaction equation

HRID 1408171 reaction equation
[CH3:1][N:2]([CH2:46][CH2:47][N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1)[C:3](=[O:45])[C:4]1[CH:44]=[CH:43][CH:42]=[C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:12][C:11]=2[C:22]2[CH:27]=[C:26]([C:28](=[O:41])[NH:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=3)[CH:25]=[CH:24][N:23]=2)=[O:8])[CH:5]=1.C(N(CC)CC)C.[C:61](Cl)(=[O:63])[CH3:62]>ClCCl>[C:61]([N:51]1[CH2:52][CH2:53][N:48]([CH2:47][CH2:46][N:2]([CH3:1])[C:3](=[O:45])[C:4]2[CH:44]=[CH:43][CH:42]=[C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]4)=[CH:12][C:11]=3[C:22]3[CH:27]=[C:26]([C:28](=[O:41])[NH:29][CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:39])([F:40])[F:38])[CH:32]=4)[CH:25]=[CH:24][N:23]=3)=[O:8])[CH:5]=2)[CH2:49][CH2:50]1)(=[O:63])[CH3:62]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 66588053HCID 66588053, compound

Product 1

HCID 66588054HCID 66588054, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Into a 50-mL round-bottom flask, was placed a solution of N1-methyl-N1-(2-(piperazin-1-yl)ethyl)-N3-(4-(piperidin-1-yl)-2-(4-(3-(trifluoromethyl)benzylcarbamoyl)pyridin-2-yl)phenyl)-isophthalamide (150 mg, 0.21 mmol, 1.00 equiv) in dichloromethane (3 mL), and triethylamine (63 mg, 0.62 mmol, 3.00 equiv). This was followed by dropwise addition of acetyl chloride (25 mg, 0.32 mmol, 1.50 equiv) with stirring at 0° C. The resulting solution was stirred for 2 h at 25° C. The reaction was then quenched with 3 mL of water. The resulting solution was extracted with 2×5 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 1×5 mL of sodium bicarbonate and 2×5 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (130 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 56.5 mg (38%) of a light yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.96 (d, J=5.1 Hz, 1H), 8.70 (d, J=9.0 Hz, 1H), 8.43 (s, 1H), 8.16˜8.08 (m, 3H), 7.87˜7.86 (m, 1H), 7.79˜7.56 (m, 7H), 4.71 (s, 2H), 4.00˜3.89 (m, 5H), 3.63˜3.52 (m, 1H), 3.23 (s, 3H), 2.17 (s, 3H), 2.01 (s, 1H), 1.81 (d, J=4.8 Hz, 1H). MS (ES, m/z): 770 [M+H]+.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. stirringThe resulting solution was stirred for 2 h at 25° C
  3. customThe reaction was then quenched with 3 mL of water
  4. extractionThe resulting solution was extracted with 2×5 mL of dichloromethane
  5. washThe resulting mixture was washed with 1×5 mL of sodium bicarbonate and 2×5 mL of brine
  6. dry with materialThe mixture was dried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe crude product (130 mg) was purified by reverse phase HPLC
  9. washeluting with a water/CH3CN gradient
  10. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-a6bef67ed2a445dab415c2eaf33de75e
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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