Potassium Carbonate → HCID 68751294, compound

HRID 1038858Notes

Reaction equation

HRID 1038858 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:11][CH:12]2[CH2:14][CH2:13]2)[C:5]2[O:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[NH2:15][C:16]1[CH:24]=[C:23]2[C:19]([C:20]([CH3:27])([CH3:26])[C:21](=[O:25])[NH:22]2)=[CH:18][CH:17]=1.C([O-])([O-])=O.[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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]>[CH:12]1([NH:11][C:4]2[C:5]3[O:10][CH:9]=[CH:8][C:6]=3[N:7]=[C:2]([NH:15][C:16]3[CH:24]=[C:23]4[C:19]([C:20]([CH3:27])([CH3:26])[C:21](=[O:25])[NH:22]4)=[CH:18][CH:17]=3)[N:3]=2)[CH2:14][CH2:13]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 135892296-Amino-3,3-dimethyl-1,3-dihydro-2H-indol-2-oneHCID 866650932-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine

Product 1

HCID 68751294HCID 68751294, compoundYield 26.1%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

To a flask was added 2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine (0.45 g, 2.14 mmol, Example #3, Step C), 6-amino-3,3-dimethylindolin-2-one (0.378 g, 2.14 mmol, Astatech), K2CO3 (0.89 g, 6.44 mmol) and t-AmOH (5 mL). To the mixture was added Pd2dba3 (0.118 g, 0.129 mmol) and X-Phos (0.123 g, 0.258 mmol). The mixture was heated to about 100° C. and stirred for about 15 h. The mixture was filtered and the filtrate was directly purified by column chromatography eluting with 0 to 70% of 10% MeOH/DCM (containing 2M 1.5% NH3 in EtOH) and DCM (25 g silica gel)). The material was then dried in a vacuum oven at about 65° C. for about 48 h. The solid was then suspended in Et2O (5 mL), sonicated for 2 min and filtered. The solid was dried in a vacuum oven at about 80° C. for about 16 h to give 6-(4-(cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-3,3-dimethylindolin-2-one (0.195 g, 26%): LC/MS (Table 2, Method c) Rt=1.81 min.; MS m/z: 350 (M+H)+. Syk IC50=A

Workup

  1. filtrationThe mixture was filtered
  2. customthe filtrate was directly purified by column chromatography
  3. washeluting with 0 to 70% of 10% MeOH/DCM (containing 2M 1.5% NH3 in EtOH) and DCM (25 g silica gel))
  4. customThe material was then dried in a vacuum oven at about 65° C. for about 48 h
  5. customsonicated for 2 min
  6. filtrationfiltered
  7. customThe solid was dried in a vacuum oven at about 80° C. for about 16 h

Sources & evidence

ORD record
ord-79555285fad24c58a1ee85a96c3226a2
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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