Acetonitrile → (S)-2-amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(2-(4-methyl-thiophen-3-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl)-propionic acid

HRID 1988010노트

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HRID 1988010 반응식
Cl[C:2]1[CH:7]=[C:6]([O:8][CH:9]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]2[C:24]([CH3:25])=[CH:23][S:22][CH:21]=2)[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH2:26])[N:3]=1.B([C:30]1[CH:41]=[CH:40][C:33]([CH2:34][C@@H:35]([C:37]([OH:39])=[O:38])[NH2:36])=[CH:32][CH:31]=1)(O)O.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>[NH2:36][C@@H:35]([CH2:34][C:33]1[CH:40]=[CH:41][C:30]([C:2]2[CH:7]=[C:6]([O:8][CH:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]3[C:24]([CH3:25])=[CH:23][S:22][CH:21]=3)[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH2:26])[N:3]=2)=[CH:31][CH:32]=1)[C:37]([OH:39])=[O:38]

참가 물질

7

반응물 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 150315L-p-BoronophenylalanineHCID 866210844-Chloro-6-{2,2,2-trifluoro-1-[2-(4-methyl-thiophen-3-yl)-phenyl]-ethoxy}-pyrimidin-2-ylamine

생성물 1

HCID 25025099(S)-2-amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(2-(4-methyl-thiophen-3-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl)-propionic acid수율 38.1%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매

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온도
150 °C

실험 절차

In a microwave vial, 4-chloro-6-{2,2,2-trifluoro-1-[2-(4-methyl-thiophen-3-yl)-phenyl]-ethoxy}-pyrimidin-2-ylamine (30 mg, 0.075 mmol), 4-borono-L-phenylalanine (19 mg, 0.09 mmol), 1 ml of actonitrile and 0.7 ml of water were mixed. 0.3 ml of 1N aqueous sodium carbonate was added to mixture, followed by 5 mole percent of dichlorobis-(triphenylphosphine)-palladium(II). The reaction vessel was sealed and heated at 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 then was purified by Prep HPLC to give 15.1 mg of (S)-2-amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(2-(4-methyl-thiophen-3-yl)-phenyl]-ethoxy}-pyrimidin-4-yl}-phenyl)-propionic acid. 1H NMR (400 MHz, CD3OD) δ (ppm) 7.94 (d, J=8 Hz, 2H), 7.80 (s, 1H), 7.50 (m, 5H), 7.25 (m, 2H), 7.03 (s, 1H), 6.94 (s, 1H), 4.31 (t, J=5.6, 1H), 3.48 (m, 1H), 3.26 (m, 1H), 1.98 (s, 3H).

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. customwas purified by Prep HPLC

출처 및 근거

ORD 기록
ord-503827162e2445e1b5bc8feb4a388181
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07553840B2

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