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 717798노트

반응식

HRID 717798 반응식
[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]

참가 물질

5

반응물 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 673785662-methyl-N-(pyridin-4-ylmethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-6-amine

생성물 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)acetamide수율 189.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-459a143de8b4440c88c7fc03c11ff11a
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09193728B2

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