Lithium Hydroxide → (S)-2-(4-(5-(5-(2-ethyl-4-(oxetan-3-yl)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-hexahydropyrazino[1,2-a]indol-1(2H)-one

HRID 1021708Notes

Reaction equation

HRID 1021708 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:39]2[CH2:51][CH2:50][N:42]3[C:43]4[CH2:44][CH2:45][CH2:46][CH2:47][C:48]=4[CH:49]=[C:41]3[C:40]2=[O:52])=[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]([CH:31]4[CH2:34][O:33][CH2:32]4)[CH2:27][C@@H:26]3[CH2:35][CH3:36])=[CH:21][N:20]=2)[C:15](=[O:37])[N:14]([CH3:38])[CH:13]=1)(=O)C.[Li+].[OH-]>CC(O)C.C1COCC1.O>[CH2:35]([C@H:26]1[CH2:27][N:28]([CH:31]2[CH2:32][O:33][CH2:34]2)[CH2:29][CH2:30][N:25]1[C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:16]2[C:15](=[O:37])[N:14]([CH3:38])[CH:13]=[C:12]([C:11]3[CH:10]=[CH:9][N:8]=[C:7]([N:39]4[CH2:51][CH2:50][N:42]5[C:43]6[CH2:44][CH2:45][CH2:46][CH2:47][C:48]=6[CH:49]=[C:41]5[C:40]4=[O:52])[C:6]=3[CH2:5][OH:4])[CH:17]=2)=[N:20][CH:21]=1)[CH3:36]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86684232(S)-(4-(5-(5-(2-ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-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 86684231(S)-2-(4-(5-(5-(2-ethyl-4-(oxetan-3-yl)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-hexahydropyrazino[1,2-a]indol-1(2H)-oneYield 25%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 131a (150 mg, 0.21 mmol) and LiOH (50 mg, 2.1 mmol) in iPrOH/THF (1:1, 4 mL) and H2O (1 mL) was stirred at 30° C. for 1 h. The mixture was evaporated in vacuo and the residue was extracted with EtOAc (10 mL×2). The combined EtOAc extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 131 (26 mg, 25%) as a white solid. LCMS: [M+H]+ 665. 1H NMR (500 MHz, CDCl3) δ 8.64 (d, J=2.0, 1H), 8.50 (d, J=5.0, 1H), 7.93 (d, J=2.5, 1H), 7.83 (d, J=1.5, 2H), 7.38 (d, J=5.0, 1H), 7.27 (d, J=5.0, 1H), 6.90 (s, 1H), 6.83 (d, J=8.5, 1H), 4.73-4.64 (m, 5H), 4.50 (s, 1H), 4.33-4.31 (m, 1H), 4.20-4.16 (m, 2H), 3.88-3.86 (m, 1H), 3.73 (s, 3H), 3.53-3.51 (m, 1H), 3.33 (s, 1H), 3.13 (t, J=5.0, 2H), 2.61-2.56 (m, 4H), 2.45 (d, J=4.0, 2H), 2.37 (s, 1H), 1.91-1.79 (m, 7H), 1.39-1.40 (m, 1H), 0.83 (t, J=7.0, 3H).

Workup

  1. customThe mixture was evaporated in vacuo
  2. extractionthe residue was extracted with EtOAc (10 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-9912a5578f584006bf6c97a3d9577a3e
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

Loading…