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

HRID 1487681Notes

Reaction equation

HRID 1487681 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:30][CH:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)[C:5]2[C:10]([C:11]3[CH:20]=[C:19]([F:21])[C:14]4[N:15]=[C:16]([CH3:18])[O:17][C:13]=4[CH:12]=3)=[CH:9][N:8]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:6]=2[N:7]=1.[NH2:36][C:37]1[CH:46]=[CH:45][C:40]([C:41]([NH:43][CH3:44])=[O:42])=[CH:39][C:38]=1[O:47][CH3:48].CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1>O1CCOCC1>[CH:31]1([O:30][C:4]2[C:5]3[C:10]([C:11]4[CH:20]=[C:19]([F:21])[C:14]5[N:15]=[C:16]([CH3:18])[O:17][C:13]=5[CH:12]=4)=[CH:9][N:8]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:6]=3[N:7]=[C:2]([NH:36][C:37]3[CH:46]=[CH:45][C:40]([C:41]([NH:43][CH3:44])=[O:42])=[CH:39][C:38]=3[O:47][CH3:48])[N:3]=2)[CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 204444344-Amino-3-methoxy-N-methylbenzamideHCID 25112535BrettphosHCID 867265066-(2-Chloro-4-(cyclopentyloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2-methylbenzo[d]oxazole

Product 1

HCID 867265084-((4-(Cyclopentyloxy)-5-(4-fluoro-2-methylbenzo[d]oxazol-6-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-N-methylbenzamideYield 63%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-(2-chloro-4-(cyclopentyloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2-methylbenzo[d]oxazole (1 equiv), 4-amino-3-methoxy-N-methylbenzamide (1.2 equiv), brettphos (0.15 equiv), cesium carbonate (3 equiv), and dicyclohexyl(2′,6′-diisopropoxy-[1,1′-biphenyl]-2-yl)phosphine (0.15 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 (63% yield). MS (ESI) m/z 661.5 [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-74e04a6a6a954fd886c48f7cb3364ae6
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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