Lithium Hydroxide → 2-(4-(5-(5-(4-(2-Hydroxyethyl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-3-(hydroxymethyl)pyridin-2-yl)-3,4,6,7,8,9-hexahydro-pyrazino[1,2-a]indol-1(2H)-one

HRID 592612Notes

Reaction equation

HRID 592612 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:36]2[CH2:48][CH2:47][N:39]3[C:40]4[CH2:41][CH2:42][CH2:43][CH2:44][C:45]=4[CH:46]=[C:38]3[C:37]2=[O:49])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH2:30][CH2:29][N:28]([CH2:31][CH2:32][OH:33])[CH2:27][CH2:26]3)=[CH:21][N:20]=2)[C:15](=[O:34])[N:14]([CH3:35])[CH:13]=1)(=O)C.[Li+].[OH-]>CC(O)C.C1COCC1.O>[OH:33][CH2:32][CH2:31][N:28]1[CH2:29][CH2:30][N:25]([C:22]2[CH:23]=[CH:24][C:19]([NH:18][C:16]3[C:15](=[O:34])[N:14]([CH3:35])[CH:13]=[C:12]([C:11]4[CH:10]=[CH:9][N:8]=[C:7]([N:36]5[CH2:48][CH2:47][N:39]6[C:40]7[CH2:41][CH2:42][CH2:43][CH2:44][C:45]=7[CH:46]=[C:38]6[C:37]5=[O:49])[C:6]=4[CH2:5][OH:4])[CH:17]=3)=[N:20][CH:21]=2)[CH2:26][CH2:27]1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86684218(4-(5-(5-(4-(2-Hydroxyethyl)piperazin-1-yl)pyridin-2-yl amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-3-yl)methyl acetate

Product 1

HCID 866842192-(4-(5-(5-(4-(2-Hydroxyethyl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-3-(hydroxymethyl)pyridin-2-yl)-3,4,6,7,8,9-hexahydro-pyrazino[1,2-a]indol-1(2H)-oneYield 31%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
35 °C

Procedure

A mixture of 123d (187 mg, 0.28 mmol) and LiOH (235 mg, 5.6 mmol) in iPrOH/THF (1:1, 3.5 mL) and H2O (0.5 mL) was stirred at 35° C. for 0.5 h. It was then evaporated in vacuo and the residue was extracted with EtOAc (5 mL×2). The combined EtOAc extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 123 (40 mg, 31%) as a yellow solid. MS: [M+H]+ 625.4. 1H NMR (500 MHz, CDCl3) δ 8.63 (d, J=2.5, 1H), 8.49 (d, J=5.0, 1H), 7.92 (d, J=2.5, 1H), 7.82 (d, J=2.0, 1H), 7.78 (s, 1H), 7.36 (d, J=5.5, 1H), 7.27-7.25 (m, 1H), 6.89 (s, 1H), 6.81 (d, J=9.5, 1H), 5.04-5.02 (m, 1H), 4.62 (d, J=10, 1H), 4.50-4.47 (m, 1H), 4.34-4.29 (m, 1H), 4.12-4.09 (m, 2H), 3.89-3.85 (m, 1H), 3.71-3.67 (m, 5H), 3.15-3.12 (m, 4H), 2.74-2.54 (m, 10H), 1.92-1.87 (m, 2H), 1.79-1.78 (m, 3H)

Workup

  1. customIt was then evaporated in vacuo
  2. extractionthe residue was extracted with EtOAc (5 mL×2)
  3. extractionThe combined EtOAc extract
  4. concentrationwas concentrated under reduced pressure
  5. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-fe58da753f3f4809a1c5efe90e578ae2
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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