Tricyclohexylphosphine → Tert-butyl 4-[6-[6-(5-amino-6-methyl-pyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-1,4-diazepane-1-carboxylate

HRID 57912

Reaction equation

HRID 57912 reaction equation
C([Sn](CCCC)(CCCC)[C:6]1[N:11]=[CH:10][C:9]2[CH:12]=[N:13][N:14]([C:15]3[N:20]=[C:19]([N:21]4[CH2:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][CH2:22]4)[CH:18]=[CH:17][CH:16]=3)[C:8]=2[CH:7]=1)CCC.Br[C:44]1[N:45]=[C:46]([CH3:51])[C:47]([NH2:50])=[N:48][CH:49]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>CN(C)C(=O)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]>[NH2:50][C:47]1[N:48]=[CH:49][C:44]([C:6]2[N:11]=[CH:10][C:9]3[CH:12]=[N:13][N:14]([C:15]4[N:20]=[C:19]([N:21]5[CH2:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:33])([CH3:34])[CH3:32])=[O:29])[CH2:23][CH2:22]5)[CH:18]=[CH:17][CH:16]=4)[C:8]=3[CH:7]=2)=[N:45][C:46]=1[CH3:51]

Participants

6

Reactant 3

HCID 75806TricyclohexylphosphineHCID 217851475-Bromo-3-methylpyrazin-2-amineHCID 86707105Tert-butyl 4-[6-(6-tributylstannylpyrazolo[4,3-c]pyridin-1-yl)-2-pyridyl]-1,4-diazepane-1-carboxylate

Product 1

HCID 86707104Tert-butyl 4-[6-[6-(5-amino-6-methyl-pyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-1,4-diazepane-1-carboxylateYield 39.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of tert-butyl 4-[6-(6-tributylstannylpyrazolo[4,3-c]pyridin-1-yl)-2-pyridyl]-1,4-diazepane-1-carboxylate (0.5852 mmol; 400 mg), 5-bromo-3-methyl-pyrazin-2-amine (1.170 mmol; 220.1 mg), tricyclohexylphosphine (0.1405 mmol; 39.39 mg) and tris(dibenzylideneacetone)dipalladium (0) (0.05852 mmol; 53.59 mg) in N,N-Dimethylacetamide (30 mL) was purged with Argon for 1 min. The reaction mixture was sealed in a Biotage microwave tube and heated under microwave at 150° C. for 45 min. The mixture was partitioned between EtOAc and water. The organic layer was concentrated and the residue was purified on silica eluted with 10% MeOH in DCM to afford tert-butyl 4-[6-[6-(5-amino-6-methyl-pyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-1,4-diazepane-1-carboxylate (115.0 mg, 39%).

Workup

  1. customwas purged with Argon for 1 min
  2. customThe reaction mixture was sealed in a Biotage microwave tube
  3. customThe mixture was partitioned between EtOAc and water
  4. concentrationThe organic layer was concentrated
  5. customthe residue was purified on silica
  6. washeluted with 10% MeOH in DCM

Sources & evidence

ORD record
ord-5e26c7d8eabe4204b7cc572e8a074ad8
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Linked notes

Loading…