Cyclopropylamine → (S)-N-cyclopropyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzamide

HRID 69597Notes

Reaction equation

HRID 69597 reaction equation
[O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:19]4[CH:27]=[CH:26][C:22]([C:23]([OH:25])=O)=[CH:21][CH:20]=4)[CH2:15][CH2:14]3)[CH:10]=[N:11][C:5]=2[N:4]2[CH2:28][CH2:29][CH2:30][C@@H:3]12.[CH:31]1([NH2:34])[CH2:33][CH2:32]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH:31]1([NH:34][C:23](=[O:25])[C:22]2[CH:26]=[CH:27][C:19]([N:16]3[CH2:17][CH2:18][N:13]([CH2:12][C:9]4[CH:10]=[N:11][C:5]5[N:4]6[CH2:28][CH2:29][CH2:30][C@H:3]6[C:2](=[O:1])[NH:7][C:6]=5[CH:8]=4)[CH2:14][CH2:15]3)=[CH:20][CH:21]=2)[CH2:33][CH2:32]1

Participants

6

Reactant 4

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58324409(S)-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzoic acid

Product 1

HCID 46864876(S)-N-cyclopropyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzamideYield 45.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzoic acid (87 mg, 0.214 mmol) and cyclopropanamine (18.29 mg, 0.320 mmol) were suspended in DMF (1 ml) and treated with DIPEA (0.186 ml, 1.068 mmol) and 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (162 mg, 0.427 mmol). The reaction mixture was stirred at room temperature for 3 h and purified using HPLC (25-95% acetonitrile in water, NH4HCO3 buffered) to afford (S)—N-cyclopropyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzamide (43.0 mg, 0.096 mmol, 45.1% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 0.46-0.59 (m, 2 H) 0.59-0.71 (m, 2 H) 1.82-2.02 (m, 3 H) 2.10-2.25 (m, 1 H) 2.46 (br. s., 4 H) 2.74-2.83 (m, 1 H) 3.21 (br. s., 4 H) 3.34-3.46 (m, 3 H) 3.53-3.64 (m, 1 H) 3.94-4.02 (m, 1 H) 6.91 (d, J=8.84 Hz, 2 H) 6.98 (d, J=1.77 Hz, 1 H) 7.61 (d, J=1.26 Hz, 1 H) 7.68 (d, J=8.84 Hz, 2 H) 8.13 (d, J=4.04 Hz, 1 H) 10.44 (s, 1 H); [M+H] calc'd for C25H30N6O2, 447; found, 447; melting point 265-268° C.

Workup

  1. custompurified

Sources & evidence

ORD record
ord-253a854ac36d4ff3a219b0a4484f35d8
Source dataset
uspto-grants-2014_09
Patent number
US08822470B2

Reaction notes

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