Dimethylformamide → (R)-N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1-(3-methyl-1H-pyrazol-1-yl)cyclopropanecarboxamide

HRID 931205Notes

Reaction equation

HRID 931205 reaction equation
Cl.Cl.[NH2:3][C:4]1[CH:5]=[CH:6][C:7]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]([N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[O:18])[CH2:12]2)=[N:8][C:9]=1[NH2:10].[CH:24]([N:27]([CH:30]([CH3:32])[CH3:31])[CH2:28][CH3:29])([CH3:26])[CH3:25].F[P-](F)(F)(F)(F)F.[N:40]1([O:49][C:50](N(C)C)=[N+](C)C)[C:44]2N=CC=C[C:43]=2N=N1.[CH3:57][N:58](C)[CH:59]=[O:60]>>[NH2:10][C:9]1[C:4]([NH:3][C:59]([C:30]2([N:27]3[CH:28]=[CH:29][C:44]([CH3:43])=[N:40]3)[CH2:31][CH2:32]2)=[O:60])=[CH:5][CH:6]=[C:7]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]([N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[O:18])[CH2:12]2)[N:8]=1.[NH2:10][C:9]1[C:4]([NH:3][C:50]([C:30]2([N:27]3[C:24]([CH3:25])=[CH:26][CH:57]=[N:58]3)[CH2:31][CH2:32]2)=[O:49])=[CH:5][CH:6]=[C:7]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]([N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[O:18])[CH2:12]2)[N:8]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89854051(R)-(1-(5,6-Diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride2×

Product 2

HCID 117966453(R)-N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1-(3-methyl-1H-pyrazol-1-yl)cyclopropanecarboxamideHCID 117966530(R)-N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1-(5-methyl-1H-pyrazol-1-yl)cyclopropanecarboxamide

Procedure

Into a vial was added Intermediate 10 (60.0 mg, 0.361 mmol), (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (Intermediate 1) (131 mg, 0.361 mmol), diisopropylethyl amine (314 μL, 1.80 mmol), O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′,-tetramethyluronium hexafluorophosphate (HATU) (206 mg, 0.541 mmol), and N,N-dimethylformamide (3.0 mL). The reaction mixture was stirred at room temperature for 2 h. The mixture was purified via flash chromatography (0-6% methanol in dichloromethane) to afford (R)—N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1-(3-methyl-1H-pyrazol-1-yl)cyclopropanecarboxamide or (R)—N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1-(5-methyl-1H-pyrazol-1-yl)cyclopropanecarboxamide (62 mg).

Workup

  1. customThe mixture was purified via flash chromatography (0-6% methanol in dichloromethane)

Sources & evidence

ORD record
ord-04b4efc3f244449e9d4759e6c878e293
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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