Cesium carbonate → (S)-N,3-Dimethyl-4-((5-(2-methylbenzo[d]oxazol-6-yl)-4-((tetrahydrofuran-3-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)benzamide

HRID 529668Notes

Reaction equation

HRID 529668 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:29][C@H:30]2[CH2:34][CH2:33][O:32][CH2:31]2)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]4[N:15]=[C:16]([CH3:18])[O:17][C:13]=4[CH:12]=3)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:6]=2[N:7]=1.[NH2:35][C:36]1[CH:45]=[CH:44][C:39]([C:40]([NH:42][CH3:43])=[O:41])=[CH:38][C:37]=1[CH3:46].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:43][NH:42][C:40](=[O:41])[C:39]1[CH:44]=[CH:45][C:36]([NH:35][C:2]2[N:3]=[C:4]([O:29][C@H:30]3[CH2:34][CH2:33][O:32][CH2:31]3)[C:5]3[C:10]([C:11]4[CH:20]=[CH:19][C:14]5[N:15]=[C:16]([CH3:18])[O:17][C:13]=5[CH:12]=4)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:27])[CH3:28])[C:6]=3[N:7]=2)=[C:37]([CH3:46])[CH:38]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 167716674-Amino-N,3-dimethylbenzamideHCID 86726440(S)-6-(2-Chloro-4-((tetrahydrofuran-3-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole

Product 1

HCID 86726441(S)-N,3-Dimethyl-4-((5-(2-methylbenzo[d]oxazol-6-yl)-4-((tetrahydrofuran-3-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)benzamideYield 63.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of (S)-6-(2-chloro-4-((tetrahydrofuran-3-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole (1 equiv), 4-amino-N,3-dimethylbenzamide (1 equiv), tris(dibenzylideneacetone)dipalladium(0) (0.1 equiv), xantphos (0.2 equiv) in 1,4-dioxane (0.1 M) was added cesium carbonate (1.4 equiv). The reaction was heated, under with microwave irradiation, in a microwave reactor at 150° C. for 2 h. The reaction mixture was quenched with saturated aqueous sodium chloride and then washed with ethyl acetate. The organic phase was combined and washed with saturated aqueous sodium chloride. The organic layer was dried (magnesium sulfate), filtered, and concentrated. The crude was purified by silica gel column chromatography (20-80% ethyl acetate, with 10% 1N ammonia in methanol in hexane). Concentration of the desired fractions afforded the title compound (63.6% yield) as a yellow solid; MS (ESI) m/z 629.4 [M+1]+.

Workup

  1. customThe reaction mixture was quenched with saturated aqueous sodium chloride
  2. washwashed with ethyl acetate
  3. washwashed with saturated aqueous sodium chloride
  4. dry with materialThe organic layer was dried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude was purified by silica gel column chromatography (20-80% ethyl acetate, with 10% 1N ammonia in methanol in hexane)

Sources & evidence

ORD record
ord-fa61660262ec41e9ac6368b5b432879c
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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