Cesium carbonate → 4-((4-(3-Cyanocyclobutoxy)-5-(4-(methylcarbamoyl)phenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-N-(oxetan-3-yl)benzamide

HRID 1487676Notes

Reaction equation

HRID 1487676 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:29][CH:30]2[CH2:33][CH:32]([C:34]#[N:35])[CH2:31]2)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]([C:15]([NH:17][CH3:18])=[O:16])=[CH:13][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.[NH2:36][C:37]1[CH:49]=[CH:48][C:40]([C:41]([NH:43][CH:44]2[CH2:47][O:46][CH2:45]2)=[O:42])=[CH:39][C:38]=1[O:50][CH3:51].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+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:34]([CH:32]1[CH2:33][CH:30]([O:29][C:4]2[C:5]3[C:10]([C:11]4[CH:20]=[CH:19][C:14]([C:15](=[O:16])[NH:17][CH3:18])=[CH:13][CH:12]=4)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:6]=3[N:7]=[C:2]([NH:36][C:37]3[CH:49]=[CH:48][C:40]([C:41]([NH:43][CH:44]4[CH2:45][O:46][CH2:47]4)=[O:42])=[CH:39][C:38]=3[O:50][CH3:51])[N:3]=2)[CH2:31]1)#[N:35]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 867264484-Amino-3-methoxy-N-(oxetan-3-yl)benzamideHCID 867265024-(2-chloro-4-(3-cyanocyclobutoxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamide

Product 1

HCID 867265034-((4-(3-Cyanocyclobutoxy)-5-(4-(methylcarbamoyl)phenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-N-(oxetan-3-yl)benzamideYield 55%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A mixture of 4-(2-chloro-4-(3-cyanocyclobutoxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamide (1 equiv), 4-amino-3-methoxy-N-(oxetan-3-yl)benzamide (1.2 equiv), 2,2′-Bis(diphenylphosphino)-1,1′-binapthalene (0.2 equiv), cesium carbonate (5 equiv), and palladium acetate (0.1 equiv) in 1,4-dioxane (0.2 M) was purged with nitrogen and sealed. The reaction mixture was heated to 110° C. for 2 h. The reaction was filtered and solvents were removed under reduced pressure. The reaction mixture was purified using silica gel chromatography (0 to 100% ethyl acetate in hexane) to give the title compound (55% yield). MS (ESI) m/z 698.4 [M+H]+.

Workup

  1. customwas purged with nitrogen
  2. customsealed
  3. filtrationThe reaction was filtered
  4. customsolvents were removed under reduced pressure
  5. customThe reaction mixture was purified

Sources & evidence

ORD record
ord-766509a8b5544808bf72306b9e58410e
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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