Acetyl chloride → HCID 44177714, compound

HRID 340406Notes

Reaction equation

HRID 340406 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][N:8]2[CH2:13][CH2:12][CH:11]([NH:14][C:15]([C:17]3[CH:25]=[CH:24][C:23]4[NH:22][C:21]5[CH2:26][CH2:27][N:28]([CH2:30][C:31]6[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=6)[CH2:29][C:20]=5[C:19]=4[CH:18]=3)=[O:16])[CH2:10][CH2:9]2)[CH:2]=1.[H-].[Na+].[C:43](Cl)(=[O:45])[CH3:44]>CN(C=O)C>[C:43]([N:22]1[C:23]2[CH:24]=[CH:25][C:17]([C:15]([NH:14][CH:11]3[CH2:12][CH2:13][N:8]([CH2:7][C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)[CH2:9][CH2:10]3)=[O:16])=[CH:18][C:19]=2[C:20]2[CH2:29][N:28]([CH2:30][C:31]3[CH:32]=[CH:33][C:34]([C:37]([F:39])([F:40])[F:38])=[CH:35][CH:36]=3)[CH2:27][CH2:26][C:21]1=2)(=[O:45])[CH3:44]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 24758Sodium hydrideHCID 44177510HCID 44177510, compound2×

Product 1

HCID 44177714HCID 44177714, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-25 °C

Procedure

To a solution of N-(1-(pyridin-3-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide (Compound 11, 50 mg, 0.09 mmol) in DMF (1.0 mL), NaH (60%, 5 mg, 0.13 mmol) was added at room temperature. The resulting brown reaction mixture was allowed to stir for 20 min, cooled down to −25° C. and acetyl chloride (7 μL, 7.7 mg, 0.1 mmol) was added. The reaction mixture was then allowed to warm up to room temperature over 1 h and poured over ice-cold saturated NaHCO3 solution to give a brown precipitate which was collected and purified by reverse phase HPLC. The purified material was triturated with ethyl ether to provide 5-acetyl-N-(1-(pyridin-3-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide (Compound 20) as its bistrifluoroacetate salt as a white solid (31%). 1H NMR (CD3OD, 300 MHz) 8.73 (d, J=1.7 Hz, 1H), 8.70 (dd, J=5.1, 1.5 Hz, 1H), 8.14 (d, J=8.8 Hz, 1H), 8.07 (dt, J=7.4, 1.7 Hz, 1H), 7.97 (s, 1H), 7.87-7.79 (m, 5H), 7.61 (dd, J=8.0, 5.0 Hz, 1H), 4.69 (s, 2H), 4.53 (s, 2H), 4.45 (s, 2H), 4.26-4.14 (m, 1H), 3.77 (br s, 2H), 3.64-3.52 (m, 4H), 3.28-3.20 (m, 2H), 2.80 (s, 3H), 2.26 (d, J=14.4 Hz, 2H), 1.99 (br s, 2H) ppm; MS (ES) 590 (M+H).

Workup

  1. temperatureto warm up to room temperature over 1 h
  2. additionpoured over ice-cold saturated NaHCO3 solution
  3. customto give a brown precipitate which
  4. customwas collected
  5. custompurified by reverse phase HPLC
  6. customThe purified material was triturated with ethyl ether

Sources & evidence

ORD record
ord-631482be4a60440481274217170e60a5
Source dataset
uspto-grants-2014_11
Patent number
US08895578B2

Reaction notes

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