Cesium carbonate → HCID 178480803, compound

HRID 577707Notes

Reaction equation

HRID 577707 reaction equation
[C:1]([O:5][C:6](=[O:37])[NH:7][C@H:8]1[CH2:11][C@H:10]([O:12][C:13]2[C:14]3[C:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)=[CH:21][N:20]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[C:15]=3[N:16]=[C:17](Cl)[N:18]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:38][N:39]1[CH:43]=[C:42]([NH2:44])[CH:41]=[N:40]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>O1CCOCC1.CCOC(C)=O.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].CO>[CH3:38][N:39]1[CH:43]=[C:42]([NH:44][C:17]2[N:18]=[C:13]([O:12][C@H:10]3[CH2:11][C@H:8]([NH:7][C:6](=[O:37])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:9]3)[C:14]3[C:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)=[CH:21][N:20]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[C:15]=3[N:16]=2)[CH:41]=[N:40]1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 47709901-methyl-1H-pyrazol-4-amineHCID 178454130HCID 178454130, compound

Product 1

HCID 178480803HCID 178480803, compoundYield 75%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution tert-butyl(trans-3-{[2-chloro-5-(pyridin-2-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy}cyclobutyl)carbamate (439 mg, 0.804 mmol) in 1,4-dioxane (8 mL) in a microwave vial was added 1-methyl-1H-pyrazol-4-amine (78.1 mg, 0.804 mmol) followed by cesium carbonate (524 mg, 1.61 mmol), tris(dibenzylideneacetone)dipalladium(0) (73.3 mg, 0.08 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (46.3 mg, 0.08 mmol) and the resulting mixture heated in the microwave to 140° C. for 45 minutes. The reaction was cooled to rt, filtered through a celite plug and stripped to a dark oil that was purified via flash chromatography (20%-100% EtOAc I heptane, then 10% methanol in EtOAc) to afford the title compound as a tan solid (365 mg, 75% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.03-9.14 (m, 1H) 8.44-8.55 (m, 1H) 8.00-8.09 (m, 1H) 7.81-7.92 (m, 1H) 7.74-7.80 (m, 1H) 7.57-7.64 (m, 1H) 7.42-7.48 (m, 1H) 7.21-7.32 (m, 1H) 7.11-7.20 (m, 1H) 5.45-5.53 (m, 2H) 5.35-5.42 (m, 1H) 4.02-4.15 (m, 1H) 3.74 (s, 3H) 3.45-3.56 (m, 2H) 2.28-2.39 (m, 4H) 1.31 (s, 9H) 0.74-0.81 (m, 2H) −0.20 (s, 9H). m/z (APCI+) for C30H42N8O4Si 607.2 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to rt
  2. filtrationfiltered through a celite plug
  3. customwas purified via flash chromatography (20%-100% EtOAc I heptane

Sources & evidence

ORD record
ord-5b528784ccde4feaa8268c8f369a91d2
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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