Cesium carbonate → 4-(4-Isopropoxy-5-(2-methylbenzo[d]oxazol-6-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-3-methoxy-N-methylbenzamide

HRID 529664Notes

Reaction equation

HRID 529664 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:29][CH:30]([CH3:32])[CH3:31])[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.[NH2:33][C:34]1[CH:43]=[CH:42][C:37]([C:38]([NH:40][CH3:41])=[O:39])=[CH:36][C:35]=1[O:44][CH3:45].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH:30]([O:29][C:4]1[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]=[C:2]([NH:33][C:34]2[CH:43]=[CH:42][C:37]([C:38]([NH:40][CH3:41])=[O:39])=[CH:36][C:35]=2[O:44][CH3:45])[N:3]=1)([CH3:32])[CH3:31]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 204444344-Amino-3-methoxy-N-methylbenzamideHCID 867264386-(2-Chloro-4-isopropoxy-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole

Product 1

HCID 867264394-(4-Isopropoxy-5-(2-methylbenzo[d]oxazol-6-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-3-methoxy-N-methylbenzamideYield 82%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

6-(2-Chloro-4-isopropoxy-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole (1 equiv), 4-amino-3-methoxy-N-methylbenzamide (1.2 equiv), palladium acetate (0.1 equiv), 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (0.2 equiv), cesium carbonate (5 equiv), and 1,4-dioxane (0.14 M) were combined and allowed to stir at 110° C. for 4 h and then cool to ambient temperature overnight. The reaction mixture was diluted with ethyl acetate and filtered through a pre-wetted (with ethyl acetate) bed of Celite. The filtrate was concentrated to an oil under reduced pressure that was purified by silica gel chromatography (0-70% ethyl acetate with 10% methanol/hexane) to afford the title compound (82% yield). MS (ESI) m/z 617.5 [M+1]+.

Workup

  1. temperaturecool to ambient temperature overnight
  2. filtrationfiltered through a pre-wetted (with ethyl acetate) bed of Celite
  3. concentrationThe filtrate was concentrated to an oil under reduced pressure that
  4. customwas purified by silica gel chromatography (0-70% ethyl acetate with 10% methanol/hexane)

Sources & evidence

ORD record
ord-3f53bd871f9e4e22bec61e7a96ee8db3
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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