Cesium carbonate → HCID 66709088, compound

HRID 475895Notes

Reaction equation

HRID 475895 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:18]2[CH2:22][CH2:21][CH2:20][CH:19]2[CH3:23])[C:5]2[CH2:10][O:9][C@@H:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.[Cl:24][C:25]1[N:26]=[CH:27][N:28]([C:30]2[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][C:31]=2[O:37][CH3:38])[CH:29]=1.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+]>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].O1CCOCC1>[Cl:24][C:25]1[N:26]=[CH:27][N:28]([C:30]2[CH:36]=[CH:35][C:33]([NH:34][C:2]3[N:3]=[C:4]([N:18]4[CH2:22][CH2:21][CH2:20][CH:19]4[CH3:23])[C:5]4[CH2:10][O:9][C@@H:8]([C:11]5[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=5)[C:6]=4[N:7]=3)=[CH:32][C:31]=2[O:37][CH3:38])[CH:29]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 580757574-(4-chloro-1H-imidazol-1-yl)-3-methoxyanilineHCID 86661660HCID 86661660, compound

Product 1

HCID 66709088HCID 66709088, compoundYield 63.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a mixture of (S)-2-chloro-7-(4-fluorophenyl)-4-(2-methylpyrrolidin-1-yl)-5,7-dihydrofuro[3,4-d]pyrimidine (Preparation Me) (192.0 mg, 0.575 mmol), 4-(4-chloro-1H-imidazol-1-yl)-3-methoxyaniline (Preparation A) (154 mg, 0.690 mmol), XANTPHOS (33.3 mg, 0.058 mmol), Pd2(dba)3 (26.3 mg, 0.029 mmol), and Cs2CO3 (562 mg, 1.726 mmol) was added Dioxane (2397 μL). The mixture was flushed with Nitrogen and placed in a capped vial and heated at 100° C. overnight. Cooled to rt and diluted with EtOAc. Filtered through a Celite® plug and rotovaped. The residue was placed on Silica Gel and eluted with an EtOAc/Hex gradient to obtain (S)—N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-7-(4-fluorophenyl)-4-(2-methylpyrrolidin-1-yl)-5,7-dihydrofuro[3,4-d]pyrimidin-2-amine (189 mg, 0.363 mmol, 63.1% yield) as a diasteriomeric mixture. The diasteriomers were separated by chiral SFC chromatography (Chiralcel OJ column, 40% MeOH (0.1% DEA) in CO2) to provide Examples 74A and 74B.

Workup

  1. customThe mixture was flushed with Nitrogen
  2. temperatureCooled to rt
  3. additiondiluted with EtOAc
  4. filtrationFiltered through a Celite® plug
  5. washeluted with an EtOAc/Hex gradient

Sources & evidence

ORD record
ord-ef4e6ec36d19401199f0a6e874b74205
Source dataset
uspto-grants-2014_01
Patent number
US08637525B2

Reaction notes

Loading…