Water → Rineterkib

HRID 596026노트

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HRID 596026 반응식
[NH2:1][C:2]1[C:3]([C:16]2[CH:48]=[CH:47][C:19]([C:20]([NH:22][C@@H:23]([C:39]3[CH:44]=[C:43]([F:45])[CH:42]=[C:41]([Br:46])[CH:40]=3)[CH2:24][N:25]([CH3:38])S(C3C=CC=CC=3[N+]([O-])=O)(=O)=O)=[O:21])=[C:18]([F:49])[CH:17]=2)=[N:4][C:5]([C@H:8]2[CH2:13][CH2:12][C@H:11]([OH:14])[C@@H:10]([F:15])[CH2:9]2)=[CH:6][N:7]=1.C([O-])([O-])=O.[K+].[K+].SC1C=CC(C(O)=O)=CC=1.O>CN(C=O)C>[NH2:1][C:2]1[C:3]([C:16]2[CH:48]=[CH:47][C:19]([C:20]([NH:22][C@@H:23]([C:39]3[CH:44]=[C:43]([F:45])[CH:42]=[C:41]([Br:46])[CH:40]=3)[CH2:24][NH:25][CH3:38])=[O:21])=[C:18]([F:49])[CH:17]=2)=[N:4][C:5]([C@H:8]2[CH2:13][CH2:12][C@H:11]([OH:14])[C@@H:10]([F:15])[CH2:9]2)=[CH:6][N:7]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 957384-Mercaptobenzoic acidHCID 1180455334-(3-Amino-6-((1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-N-((S)-1-(3-bromo-5-fluorophenyl)-2-((N-methyl-2-nitrophenyl)sulfonamido)ethyl)-2-fluorobenzamide

생성물 1

HCID 118045847Rineterkib수율 68.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
45 °C

실험 절차

To a solution of 4-(3-amino-6-((1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-N—((S)-1-(3-bromo-5-fluorophenyl)-2-(N-methyl-2-nitrophenylsulfonamido)ethyl)-2-fluorobenzamide (293 mg, 0.38 mmol) in DMF (3.8 mL) was added K2CO3 (371 mg, 2.69 mmol) and 4-mercaptobenzoic acid (207 mg, 1.34 mmol). The reaction mixture was heated in microwave synthesizer at 45° C. for 55 min. After the reaction, water was added, and the mixture was extracted with EtOAc three times. The organic layers were combined and washed with water three times. The combined organic layer was dried over sodium sulfate, filtered off, and concentrated in vacuo. The residue was purified with flash chromatography eluting with EtOAc (containing 20% MeOH and 0.5% ammonia in water)/DCM to provide 150 mg of 4-(3-amino-6-((1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-N—((S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl)-2-fluorobenzamide. LCMS (m/z): 578, 580 (MH+), 0.64 min. 1H NMR (400 MHz, CD3OD) δ ppm 7.80 (s, 1H), 7.76-7.68 (m, 1H), 7.59 (dd, J=1.6, 7.8 Hz, 1H), 7.53 (dd, J=1.2, 11.7 Hz, 1H), 7.37 (s, 1H), 7.18 (d, J=8.2 Hz, 1H), 7.11 (d, J=9.4 Hz, 1H), 5.27-5.10 (m, 1H), 4.42-4.13 (m, 1H), 3.65-3.49 (m, 1H), 2.97-2.88 (m, 1H), 2.87-2.79 (m, 1H), 2.74 (t, J=11.7 Hz, 1H), 2.35 (s, 3H), 2.22-2.11 (m, 1H), 2.04-1.92 (m, 1H), 1.85-1.68 (m, 2H), 1.55 (dq, J=3.1, 12.9 Hz, 1H), 1.46-1.33 (m, 1H).

후처리

  1. additionwas added
  2. extractionthe mixture was extracted with EtOAc three times
  3. washwashed with water three times
  4. dry with materialThe combined organic layer was dried over sodium sulfate
  5. filtrationfiltered off
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified with flash chromatography
  8. washeluting with EtOAc (containing 20% MeOH and 0.5% ammonia in water)/DCM

출처 및 근거

ORD 기록
ord-f68b980ff5da4d6dad18ab8ad6f33c05
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242996B2

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