Diisopropylethylamine → N-(2-amino-6-(3-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-3-yl)piperidin-1-yl)pyridin-3-yl)-1-(3-oxomorpholino)cyclopropanecarboxamide

HRID 931230Notes

Reaction equation

HRID 931230 reaction equation
[O:1]=[C:2]1[N:7]([C:8]2([C:11]([OH:13])=O)[CH2:10][CH2:9]2)[CH2:6][CH2:5][O:4][CH2:3]1.Cl.Cl.[NH2:16][C:17]1[CH:18]=[CH:19][C:20]([N:24]2[CH2:29][CH2:28][CH2:27][C@@H:26]([C:30]([N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)=O)[CH2:25]2)=[N:21][C:22]=1[NH2:23].F[P-](F)(F)(F)(F)F.[N:44]1(OC(N(C)C)=[N+](C)C)[C:48]2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[NH2:23][C:22]1[C:17]([NH:16][C:11]([C:8]2([N:7]3[CH2:6][CH2:5][O:4][CH2:3][C:2]3=[O:1])[CH2:9][CH2:10]2)=[O:13])=[CH:18][CH:19]=[C:20]([N:24]2[CH2:29][CH2:28][CH2:27][CH:26]([C:30]3[N:32]4[CH2:36][CH2:35][CH2:34][C:33]4=[CH:48][N:44]=3)[CH2:25]2)[N:21]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 898538621-(3-Oxomorpholin-4-yl)cyclopropane-1-carboxylic acidHCID 89854051(R)-(1-(5,6-Diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride

Product 1

HCID 117966569N-(2-amino-6-(3-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-3-yl)piperidin-1-yl)pyridin-3-yl)-1-(3-oxomorpholino)cyclopropanecarboxamideYield 94.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a vial were added 1-(3-oxomorpholino)cyclopropanecarboxylic acid (33 mg, 0.2 mmol), (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (77.5 mg, 0.2 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′,-tetramethyluronium hexafluorophosphate (135 mg, 0.4 mmol), diisopropylethyl amine (155 μL, 0.9 mmol) and N,N-dimethylformamide (3.0 mL). The reaction mixture was stirred at room temperature for 3 h. The mixture was directly loaded to a column and purified via flash chromatography (0-6% methanol in dichloromethane) to afford N-(2-amino-6-(3-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-3-yl)piperidin-1-yl)pyridin-3-yl)-1-(3-oxomorpholino)cyclopropanecarboxamide (77.0 mg, 94.7%). MS (ES+) (M+H) 457.3; LCMS retention time 1.56 min (Method L).

Workup

  1. custompurified via flash chromatography (0-6% methanol in dichloromethane)

Sources & evidence

ORD record
ord-734a19e7188548a4a71075f51a54640a
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

Loading…