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Sodium Carbonate → (4S,5S)-3-(2'-Amino-2-morpholino-4'-(trifluoromethyl)-[4,5'-bipyrimidin]-6-yl)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-5-(4-methoxyphenyl)oxazolidin-2-one

HRID 929957
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HRID 929957 반응식
[Si:1]([O:18][CH2:19][C@H:20]1[C@H:24]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[O:23][C:22](=[O:33])[N:21]1[C:34]1[CH:39]=[C:38](Cl)[N:37]=[C:36]([N:41]2[CH2:46][CH2:45][O:44][CH2:43][CH2:42]2)[N:35]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:55]2[C:56]([C:62]([F:65])([F:64])[F:63])=[N:57][C:58]([NH2:61])=[N:59][CH:60]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[NH2:61][C:58]1[N:57]=[C:56]([C:62]([F:65])([F:63])[F:64])[C:55]([C:38]2[CH:39]=[C:34]([N:21]3[C@@H:20]([CH2:19][O:18][Si:1]([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[C@H:24]([C:25]4[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=4)[O:23][C:22]3=[O:33])[N:35]=[C:36]([N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)[N:37]=2)=[CH:60][N:59]=1
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참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 574164395-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amineHCID 86718539(4S,5S)-4-(((tert-Butyldiphenylsilyl)oxy)methyl)-3-(6-chloro-2-morpholinopyrimidin-4-yl)-5-(4-methoxyphenyl)oxazolidin-2-one

생성물 1

HCID 86718540(4S,5S)-3-(2'-Amino-2-morpholino-4'-(trifluoromethyl)-[4,5'-bipyrimidin]-6-yl)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-5-(4-methoxyphenyl)oxazolidin-2-one
수율 38%

시약·촉매·용매 3

HCID 178418807HCID 178418807, 화합물촉매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of (4S,5S)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-3-(6-chloro-2-morpholinopyrimidin-4-yl)-5-(4-methoxyphenyl)oxazolidin-2-one (150 mg, 228 μmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine (108 mg, 364 μmol), 20% aqueous Na2CO3 (0.24 mL, 2.28 mmol), and PdCl2(dppf)-CH2Cl2 (18.6 mg, 23 μmol) in DME (2 mL) under argon was stirred at 80° C. for 8 h. The reaction mixture was diluted with EtOAc and washed with saturated NaHCO3 solution, H2O and brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography using EtOAc in heptane from 0% to 33% in order to give the title compound as a light yellow foam (68 mg, 28%): TLC (heptane/EtOAc 1:1) Rf=0.32; tR=1.663 min (UPLC 1); LC-MS: [M+H] 786; Rt 1.48 min; (LCMS method 2).

후처리

  1. washwashed with saturated NaHCO3 solution, H2O and brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography

출처 및 근거

ORD 기록
ord-c6038e7a09a04e0b889a92b36db51b2c
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09296733B2

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