Ethylamine hydrochloride → (S)-N-ethyl-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

HRID 716213Notes

Reaction equation

HRID 716213 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.Cl.[CH2:32]([NH2:34])[CH3:33].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>[CH2:32]([NH:34][C:23](=[O:24])[C:22]1[CH:26]=[CH:27][C:19]([N:16]2[CH2:17][CH2:18][N:13]([CH2:12][C:9]3[CH:10]=[N:11][C:5]4[N:4]5[CH2:28][CH2:29][CH2:30][C@H:3]5[C:2](=[O:1])[NH:7][C:6]=4[CH:8]=3)[CH2:14][CH2:15]2)=[N:20][CH:21]=1)[CH3:33]

Participants

6

Reactant 4

HCID 11198Ethylamine hydrochlorideHCID 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 58324388(S)-N-ethyl-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)nicotinamideYield 28.6%

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 ethanamine hydrochloride (17.4 mg, 0.213 mmol) were suspended in DMF (1.065 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-ethyl-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 (26.4 mg, 0.061 mmol, 28.5% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 1.09 (t, J=7.20 Hz, 3H) 1.82-2.02 (m, 3H) 2.18 (d, J=2.27 Hz, 1H) 2.41 (t, J=4.80 Hz, 5H) 3.20-3.29 (m, 2H) 3.34-3.44 (m, 3H) 3.51-3.63 (m, 5H) 3.95-4.03 (m, 1H) 6.82 (d, J=9.09 Hz, 1H) 6.99 (d, J=1.77 Hz, 1H) 7.61 (d, J=1.77 Hz, 1H) 7.93 (dd, J=9.09, 2.53 Hz, 1H) 8.23 (t, J=5.31 Hz, 1H) 8.57 (d, J=2.27 Hz, 1H) 10.44 (s, 1H); [M+H] calc'd for C23H29N7O2, 422. found, 422.

Workup

  1. custompurified

Sources & evidence

ORD record
ord-cce330b5b4864deab187fe9c41f2d987
Source dataset
uspto-grants-2015_11
Patent number
US09187497B2

Reaction notes

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