Benzylamine → HCID 67130069, compound

HRID 1038840Notes

Reaction equation

HRID 1038840 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:16]=[C:15]([CH:17]3[CH2:19][CH2:18]3)[NH:14][N:13]=2)[C:5]2[O:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[CH2:20]([NH2:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.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>[CH2:20]([NH:27][C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:16]=[C:15]([CH:17]3[CH2:19][CH2:18]3)[NH:14][N:13]=2)[C:5]2[O:10][CH:9]=[CH:8][C:6]=2[N:7]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 7504Benzylamine2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2×HCID 86665109HCID 86665109, compound

Product 1

HCID 67130069HCID 67130069, compoundYield 5.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

To a vial was added 2-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)furo[3,2-d]pyrimidin-4-amine (0.20 g, 0.73 mmol), benzyl amine (0.79 mL, 7.3 mmol), X-Phos (0.02 g, 0.04 mmol) K2CO3 (0.50 g, 3.6 mmol), and Pd2dba3 (0.04 g, 0.04 mmol). To the vial was added t-BuOH (3.6 mL) and tube was sealed. The tube was evacuated, purged with nitrogen three times and stirred over night at about 100° C. To the mixture was added additional benzyl amine (0.79 mL, 7.3 mmol), X-Phos (0.02 g, 0.04 mmol), and Pd2dba3 (0.04 g, 0.04 mmol). The mixture was stirred at about 100° C. for about 26 h. The mixture was filtered, the filter pad was washed with DCM and then the solvent was removed in vacuo. The crude material was added to a silica gel column and was eluted with EtOAc/DCM (50% to 100% gradient) followed by 2.0 M NH3 in EtOH/DCM (2%) to give N2-benzyl-N4-(5-cyclopropyl-1H-pyrazol-3-yl)furo[3,2-d]pyrimidine-2,4-diamine (0.013 g, 5%). LC/MS Rt=1.30 min; MS m/z 347.29 (M+H)+. Syk IC50=B.

Workup

  1. customwas sealed
  2. customThe tube was evacuated
  3. custompurged with nitrogen three times
  4. stirringThe mixture was stirred at about 100° C. for about 26 h
  5. filtrationThe mixture was filtered
  6. washthe filter pad was washed with DCM
  7. customthe solvent was removed in vacuo
  8. additionThe crude material was added to a silica gel column
  9. washwas eluted with EtOAc/DCM (50% to 100% gradient)

Sources & evidence

ORD record
ord-768b141471e44a7280fb62f2b3fd63fb
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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