Triethylamine → (S)-2-((1-(2-(3-chloro-1,2-dimethyl-1H-indol-5-ylamino)pyrimidin-4-yl)-3-methyl-1H-pyrazol-4-yl)methyl)isoxazolidin-4-ol

HRID 1503354노트

반응식

HRID 1503354 반응식
[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH:11][C:12]3[N:17]=[C:16]([N:18]4[CH:22]=[C:21]([CH:23]=O)[C:20]([CH3:25])=[N:19]4)[CH:15]=[CH:14][N:13]=3)[CH:9]=2)[N:4]([CH3:26])[C:3]=1[CH3:27].Cl.[O:29]1[CH2:33][C@@H:32]([OH:34])[CH2:31][NH:30]1.C(N(CC)CC)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCl>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH:11][C:12]3[N:17]=[C:16]([N:18]4[CH:22]=[C:21]([CH2:23][N:30]5[CH2:31][C@H:32]([OH:34])[CH2:33][O:29]5)[C:20]([CH3:25])=[N:19]4)[CH:15]=[CH:14][N:13]=3)[CH:9]=2)[N:4]([CH3:26])[C:3]=1[CH3:27]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 66855047(4S)-1,2-oxazolidin-4-ol hydrochlorideHCID 866989881-(2-(3-chloro-1,2-dimethyl-1H-indol-5-ylamino)pyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carbaldehyde

생성물 1

HCID 118022801(S)-2-((1-(2-(3-chloro-1,2-dimethyl-1H-indol-5-ylamino)pyrimidin-4-yl)-3-methyl-1H-pyrazol-4-yl)methyl)isoxazolidin-4-ol

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a slurry of Intermediate 3 (190 mg, 0.5 mmol), (S)-isoxazolidin-4-ol hydrochloride (95 mg, 0.75 mmol) and triethylamine (0.4 mL) in 10 mL of dichloromethane, was added NaBH(OAc)3 (0.32 g, 1.5 mmol) at room temperature. The reaction was stirred for 12 hour at room temperature and then quenched with 1N—NaOH. It was extracted with ethyl acetate and washed twice with brine. The collected organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting residue was purified by silica gel chromatography (DCM/MeOH) to afford desired Compound No. 31 as a pale yellow solid (159 mg, 70%); MS (ESI) m/z 454 [M+H]+. 1H NMR (300 MHz, CDCl3) δ 8.43 (s, 1H), 8.34 (d, J=5.4 Hz, 1H), 7.89 (s, 1H), 7.68 (s, 1H), 7.14-7.16 (m, 3H), 4.73 (brs, 1H), 4.23 (brs, 1H), 3.92-3.96 (m, 2H), 3.84 (brs, 1H), 3.63 (s, 3H), 3.25 (brs, 1H), 2.73 (brs, 1H), 2.40 (s, 3H), 2.36 (s, 3H

후처리

  1. customquenched with 1N—NaOH
  2. extractionIt was extracted with ethyl acetate
  3. washwashed twice with brine
  4. dry with materialThe collected organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by silica gel chromatography (DCM/MeOH)

출처 및 근거

ORD 기록
ord-bc8171de1c364cc4a8c78487e4dc1540
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09212178B2

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