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 929957Notes

Reaction equation

HRID 929957 reaction equation
[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

Participants

7

Reactant 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

Product 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-oneYield 38%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-c6038e7a09a04e0b889a92b36db51b2c
Source dataset
uspto-grants-2016_03
Patent number
US09296733B2

Reaction notes

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