Cyclopropylamine → HCID 58324458, compound

HRID 69586Notes

Reaction equation

HRID 69586 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](O)=[O:24])=[CH:21][N: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:24])[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)=[N: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 58324509(S)-6-(4((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinic acid

Product 1

HCID 58324458HCID 58324458, compoundYield 73.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-6-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinic acid (87 mg, 0.213 mmol) and cyclopropanamine (18.24 mg, 0.319 mmol) were suspended in DMF (1 ml) and treated with DIPEA (0.186 ml, 1.065 mmol) and 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (162 mg, 0.426 mmol). The reaction mixture was stirred at room temperature for 3 h and purified using HPLC (10-95% acetonitrile in water, NH4HCO3 buffered) to afford (S)—N-cyclopropyl-6-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinamide (70.3 mg, 0.157 mmol, 73.7% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 0.49-0.56 (m, 2 H) 0.62-0.70 (m, 2H) 1.82-2.02 (m, 3 H) 2.11-2.22 (m, 1 H) 2.40 (t, J=4.93 Hz, 4 H) 2.78 (tq, J=7.34, 3.86 Hz, 1H) 3.34 (br. s., 2 H) 3.36-3.44 (m, 1 H) 3.49-3.64 (m, 5 H) 3.94-4.03 (m, 1 H) 6.81 (d, J=8.59 Hz, 1 H) 6.98 (d, J=1.77 Hz, 1 H) 7.61 (d, J=1.77 Hz, 1 H) 7.90 (dd, J=9.09, 2.53 Hz, 1H) 8.20 (d, J=4.04 Hz, 1 H) 8.54 (d, J=1.77 Hz, 1 H) 10.44 (s, 1 H); [M+H] calc'd for C24H29N7O2, 448; found, 448.

Workup

  1. custompurified

Sources & evidence

ORD record
ord-c3bc7e37cfcb4662a034b5956ab1c1be
Source dataset
uspto-grants-2014_09
Patent number
US08822470B2

Reaction notes

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