Potassium Carbonate → HCID 68754980, compound

HRID 1038864Notes

Reaction equation

HRID 1038864 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]([CH:20]=[N:21][N:22]2[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[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].CC(O)(C)C>[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]([CH:20]=[N:21][N:22]4[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[CH:18][CH:17]=3)[N:3]=2)[CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 120186071-BOC-6-AMINO-INDAZOLEHCID 866650932-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine

Product 1

HCID 68754980HCID 68754980, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
85 °C

Procedure

To a flask was added 2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine (10.5 g, 50.1 mmol, Example #3, Step C), tert-butyl 6-amino-1H-indazole-1-carboxylate (14.02 g, 60.1 mmol, Frontier), K2CO3 (8.31 g, 60.1 mmol) and t-BuOH (334 mL). The reaction vessel was purged under vacuum and vented with N2 three times. To the mixture was added Pd2dba3 (2.75 g, 3.01 mmol) and X-Phos (2.87 g, 6.01 mmol). The reaction vessel was purged under vacuum and vented with N2. The mixture was heated to about 85° C. for about 3 days. The mixture was diluted with EtOAc (1000 mL) and washed with water (1000 mL). The organic layer was dried with MgSO4, filtered through a pad of Celite® and concentrated in vacuo. The residue was purified by column chromatography (300 g silica gel, DCM/MeOH 1:0 to 10:1) to give a solid. The material was further purified by column chromatography (300 g silica gel, DCM/EtOAc 1:0 to 0:1) to give tert-butyl 6-(4-(cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-1H-indazole-1-carboxylate (9.78 g, 48%): LC/MS (Table 2, Method u) Rt=1.48 min; MS m/z: 407 (M+H)+

Workup

  1. customThe reaction vessel was purged under vacuum
  2. customThe reaction vessel was purged under vacuum
  3. additionThe mixture was diluted with EtOAc (1000 mL)
  4. washwashed with water (1000 mL)
  5. dry with materialThe organic layer was dried with MgSO4
  6. filtrationfiltered through a pad of Celite®
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (300 g silica gel, DCM/MeOH 1:0 to 10:1)
  9. customto give a solid
  10. customThe material was further purified by column chromatography (300 g silica gel, DCM/EtOAc 1:0 to 0:1)

Sources & evidence

ORD record
ord-af0e5c467fb644adb0f9fc2f26282be0
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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