Chloroacetyl chloride → 2-chloro-N-(2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indol-6-yl)-N-((pyridin-4-yl)methyl)acetamide

HRID 717798Notes

Reaction equation

HRID 717798 reaction equation
[CH3:1][N:2]1[CH2:22][CH2:21][C:5]2[NH:6][C:7]3[C:12]([C:4]=2[CH2:3]1)=[CH:11][CH:10]=[CH:9][C:8]=3[NH:13][CH2:14][C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1.C(N(CC)CC)C.[Cl:30][CH2:31][C:32](Cl)=[O:33]>C(Cl)Cl>[Cl:30][CH2:31][C:32]([N:13]([C:8]1[C:7]2[NH:6][C:5]3[CH2:21][CH2:22][N:2]([CH3:1])[CH2:3][C:4]=3[C:12]=2[CH:11]=[CH:10][CH:9]=1)[CH2:14][C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)=[O:33]

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 67378566HCID 67378566, compound

Product 1

HCID 673791812-chloro-N-(2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indol-6-yl)-N-((pyridin-4-yl)methyl)acetamideYield 189.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2,3,4,5-Tetrahydro-2-methyl-N-((pyridin-4-yl)methyl)-1H-pyrido[4,3-b]indol-6-amine (0.15 g, 0.515 mmol) was dissolved in DCM (10 mL) and cooled to 0° C. Triethylamine (0.145 mL, 1.03 mmol) was added dropwise with constant stirring. 2-Chloroacetylchloride (0.04 mL, 0.515 mmol) was added dropwise at the same temperature and, after addition, allowed to come to RT. The reaction mass was stirred at RT for 20 min. Ice water (3 mL) was then added and the mixture extracted with DCM. The organic layer was washed with saturated bicarbonate solution (3 mL) to obtain 2-chloro-N-(2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indol-6-yl)-N-((pyridin-4-yl)methyl)acetamide (360 mg). The product (360 mg, 0.978 mmol) was dissolved in DMF (1 mL) and cooled to 0° C. Sodium hydride (46 mg, 1.173 mmol) was added and the reaction mixture was stirred at RT for 20 min. MeOH (2 mL) was added and concentrated under reduced pressure. The product was purified through reverse phase chromatography. Yield: 10.7 mg as freebase. 1H NMR (CD3OD, freebase) d (ppm): 8.45 (d, 2H), 7.40 (d, 2H), 7.10 (d, 1H), 6.90 (t, 1H), 6.56 (d, 1H), 5.30 (s, 2H), 5.06 (s, 2H), 4.0 (s, 2H), 3.20 (t, 2H), 3.0 (t, 2H), 2.76 (s, 3H).

Workup

  1. additionafter addition
  2. customto come to RT
  3. extractionthe mixture extracted with DCM
  4. washThe organic layer was washed with saturated bicarbonate solution (3 mL)

Sources & evidence

ORD record
ord-459a143de8b4440c88c7fc03c11ff11a
Source dataset
uspto-grants-2015_11
Patent number
US09193728B2

Reaction notes

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