Acetonitrile → (S)-3-[4-(2-amino-6-{(S)-2,2,2-trifluoro-1-[4-(5-methoxy-pyridin-3-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl]-2-tert butoxycarbonylamino-propionic acid

HRID 1988050노트

반응식

HRID 1988050 반응식
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C@H:15]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:16]([OH:18])=[O:17])=[CH:10][CH:9]=2)[CH:5]=[C:4]([O:27][C@@H:28]([C:33]2[CH:38]=[CH:37][C:36](Br)=[CH:35][CH:34]=2)[C:29]([F:32])([F:31])[F:30])[N:3]=1.[CH3:40][O:41][C:42]1[CH:43]=[N:44][CH:45]=[C:46](B2OC(C)(C)C(C)(C)O2)[CH:47]=1.C(#N)C.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C@H:15]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:16]([OH:18])=[O:17])=[CH:10][CH:9]=2)[CH:5]=[C:4]([O:27][C@@H:28]([C:33]2[CH:38]=[CH:37][C:36]([C:46]3[CH:45]=[N:44][CH:43]=[C:42]([O:41][CH3:40])[CH:47]=3)=[CH:35][CH:34]=2)[C:29]([F:32])([F:31])[F:30])[N:3]=1

참가 물질

7

반응물 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 38661613-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 66742588(S)-3-(4-{2-amino-6-[(S)-1-(4-bromo-phenyl)-2,2,2-trifluoro-ethoxy]-pyrimidin-4-yl}-phenyl)-2-tert-butoxycarbonylamino-propionic acid

생성물 1

HCID 66743754(S)-3-[4-(2-amino-6-{(S)-2,2,2-trifluoro-1-[4-(5-methoxy-pyridin-3-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl]-2-tert butoxycarbonylamino-propionic acid수율 40.8%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매

반응 조건

온도
150 °C

실험 절차

A microwave vial (2 ml) was charged with (S)-3-(4-{2-amino-6-[(S)-1-(4-bromo-phenyl)-2,2,2-trifluoro-ethoxy]-pyrimidin-4-yl}-phenyl)-2-tert-butoxycarbonylamino-propionic acid (139 mg, 0.23 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-pyridine (69 mg, 0.27 mmol), 1 ml of acetonitrile, and 0.7 ml of water. To this mixture was added 0.4 ml of aqueous sodium carbonate (1M), followed by 14 mg of dichlorobis-(triphenylphosphine)-palladium(II). The reaction vessel was sealed and heated to 150° C. for 5 minutes with microwave irradiation. After cooling, the reaction mixture was evaporated to dryness, the residue was dissolved in 2.5 ml of methanol and purified by preparative HPLC to give 60 mg of (S)-3-[4-(2-amino-6-{(S)-2,2,2-trifluoro-1-[4-(5-methoxy-pyridin-3-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl]-2-tert butoxycarbonylamino-propionic acid.

후처리

  1. customThe reaction vessel was sealed
  2. temperatureAfter cooling
  3. customthe reaction mixture was evaporated to dryness
  4. dissolutionthe residue was dissolved in 2.5 ml of methanol
  5. custompurified by preparative HPLC

출처 및 근거

ORD 기록
ord-590ec3ff8a2844f5aa5aa20a873f98d4
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07553840B2

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