Ammonia → HCID 90113020, 화합물

HRID 1508814노트

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HRID 1508814 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22](O)=[O:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([C:25]([F:28])([F:27])[F:26])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[NH3:35].CO>ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([NH2:35])=[O:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([C:25]([F:27])([F:26])[F:28])[N:9]=2)[CH:5]=[CH:6][CH:7]=1

참가 물질

7

반응물 4

HCID 222AmmoniaHCID 887MethanolHCID 65578Oxalyl chlorideHCID 90111638Zatolmilast

생성물 1

HCID 90113020HCID 90113020, 화합물수율 21%

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

An 100-mL round bottom flask was charged with 2-(4-((2-(3-chlorophenyl)-6-(trifluoromethyl)pyridin-4-yl)methyl)phenyl)acetic acid (0.17 g, 0.42 mmol) in dichloromethane (10 ml). To this solution at 0° C. was added oxalyl chloride (0.18 mL, 2.10 mmol) followed by DMF (1 drop). After stirring for 5 h the volatile material was removed under reduced pressure to afford crude acid chloride. The residue was dissolved in dichloromethane (10 mL), cooled to 0° C., and 7N ammonia in methanol (10.0 mL, 70 mmol) was added. After stirring for 0.5 h, the volatile material was removed under reduced pressure. The residue was purified by chromatography on silica using hexanes/ethyl acetate (10:0 to 0:10) as eluent followed by chromatography on silica using dichloromethane/methanol (10:0 to 9:1) as eluent to afford the title compound (0.079 g, 21%) as an off-white solid. MW=404.81. M.p. 148-160° C. 1H NMR (DMSO-d6, 500 MHz) δ 8.33 (s, 1H), 8.17-8.15 (m, 1H), 8.11-8.05 (m, 1H), 7.76 (d, J=0.5 Hz, 1H), 7.60-7.55 (m, 2H), 7.41 (br s, 1H), 7.31 (d, J=8.0 Hz, 2H), 7.21 (d, J=8.0 Hz, 2H), 6.82 (br s, 1H), 4.11 (s, 2H), 3.32 (s, 2H); APCI MS m/z 405 [M+H]+.

후처리

  1. customwas removed under reduced pressure
  2. customto afford crude acid chloride
  3. stirringAfter stirring for 0.5 h
  4. customthe volatile material was removed under reduced pressure
  5. customThe residue was purified by chromatography on silica

출처 및 근거

ORD 기록
ord-311fbe2e208e4ad4994978db81af1ce8
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221843B2

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