Lithium Hydroxide → 2-[3-(Hydroxymethyl)-4-[8-[[5-[4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-one

HRID 1024096Notes

Reaction equation

HRID 1024096 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:38]2[CH2:50][CH2:49][N:41]3[C:42]4[CH2:43][CH2:44][CH2:45][CH2:46][C:47]=4[CH:48]=[C:40]3[C:39]2=[O:51])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:13]=[C:14]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([N:28]3[CH2:33][CH2:32][N:31]([CH:34]4[CH2:37][O:36][CH2:35]4)[CH2:30][CH2:29]3)=[CH:24][N:23]=2)[C:15]2[N:16]([N:18]=[CH:19][N:20]=2)[CH:17]=1)(=O)C.[OH-].[Li+]>C(O)(C)C.C1COCC1.O>[OH:4][CH2:5][C:6]1[C:7]([N:38]2[CH2:50][CH2:49][N:41]3[C:42]4[CH2:43][CH2:44][CH2:45][CH2:46][C:47]=4[CH:48]=[C:40]3[C:39]2=[O:51])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:13]=[C:14]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([N:28]3[CH2:29][CH2:30][N:31]([CH:34]4[CH2:37][O:36][CH2:35]4)[CH2:32][CH2:33]3)=[CH:24][N:23]=2)[C:15]2[N:16]([N:18]=[CH:19][N:20]=2)[CH:17]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86684162(4-(8-(5-(4-(Oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)[1,2,4]triazolo[1,5-a]pyridin-6-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 715574732-[3-(Hydroxymethyl)-4-[8-[[5-[4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1-oneYield 38%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 122a (200 mg, 0.29 mmol) and lithium hydroxide (42 mg, 1.0 mmol) in i-propanol/THF (1:1, 3.5 mL) and water (1 mL) was stirred at 40° C. for 0.5 h. The mixture was evaporated under reduced pressure and the residue was diluted with water (5 mL). It was extracted with ethyl acetate (2×5 mL). The combined ethyl acetate extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 122 (70 mg, 38%) as pale yellow solid. MS-ESI: [M+H]+ 647.3. 1H NMR (500 MHz, DMSO-d6) δ 9.36 (s, 1H), 8.69 (s, 1H), 8.61 (s, 1H), 8.57-8.55 (m, 2H), 7.93 (d, J=2.5 Hz, 1H), 7.48-7.43 (m, 2H), 7.37-7.35 (m, 1H), 6.59 (s, 1H), 5.05 (t, J=5.0 Hz, 1H), 4.57-4.55 (m, 2H), 4.61-4.59 (m, 2H), 4.40-4.39 (m, 2H), 4.26-4.12 (m, 3H), 3.92-3.89 (m, 1H), 3.43 (t, J=6.0 Hz, 1H), 3.11-3.09 (m, 4H), 2.63-2.57 (m, 2H), 2.50-2.47 (m, 2H), 2.40-2.39 (m, 4H), 1.79-1.77 (m, 2H), 1.70-1.68 (m, 2H).

Workup

  1. customThe mixture was evaporated under reduced pressure
  2. additionthe residue was diluted with water (5 mL)
  3. extractionIt was extracted with ethyl acetate (2×5 mL)
  4. extractionThe combined ethyl acetate extract
  5. concentrationwas concentrated under reduced pressure
  6. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-5f393d3fa6b74b1a9ccd19c59169e3e1
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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