Lithium hydroxide, monohydrate → 2-(4-(5-(5-Cyclopropyl-1H-pyrazol-3-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 592595Notes

Reaction equation

HRID 592595 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:29]2[CH2:41][CH2:40][N:32]3[C:33]4[CH2:34][CH2:35][CH2:36][CH2:37][C:38]=4[CH:39]=[C:31]3[C:30]2=[O:42])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:23]=[C:22]([CH:24]3[CH2:26][CH2:25]3)[NH:21][N:20]=2)[C:15](=[O:27])[N:14]([CH3:28])[CH:13]=1)(=O)C.O[Li].O>CC(O)C.C1COCC1.O>[CH:24]1([C:22]2[NH:21][N:20]=[C:19]([NH:18][C:16]3[C:15](=[O:27])[N:14]([CH3:28])[CH:13]=[C:12]([C:11]4[CH:10]=[CH:9][N:8]=[C:7]([N:29]5[CH2:41][CH2:40][N:32]6[C:33]7[CH2:34][CH2:35][CH2:36][CH2:37][C:38]=7[CH:39]=[C:31]6[C:30]5=[O:42])[C:6]=4[CH2:5][OH:4])[CH:17]=3)[CH:23]=2)[CH2:25][CH2:26]1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86684205(4-(5-(5-Cyclopropyl-1H-pyrazol-3-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)pyridine-3-yl)methyl acetate

Product 1

HCID 715592982-(4-(5-(5-Cyclopropyl-1H-pyrazol-3-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 61.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 118c (350 mg, 0.62 mmol) and LiOH.H2O (260 mg, 6.2 mmol) in iPrOH/THF (1:1, 3 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 118 (200 mg, 54%) as a white solid. LCMS: [M+H]+ 526. 1H NMR (500 MHz, DMSO) δ 11.83 (s, 1H), 8.48 (d, J=5, 1H), 8.05 (d, J=2, 1H), 8.03 (s, 1H), 7.38 (d, J=2, 1H), 7.31 (d, J=5, 1H), 6.58 (s, 1H), 5.81 (d, J=2, 1H), 4.95 (t, J=5, 1H), 4.49-4.51 (m, 1H), 4.38-4.40 (m, 1H), 4.19-4.21 (m, 3H), 3.85-3.87 (m, 1H), 3.58 (s, 3H), 2.61-2.62 (m, 1H), 2.56-2.57 (m, 1H), 2.48-2.49 (m, 2H), 1.81-1.82 (m, 3H), 1.70-1.71 (m, 2H), 0.88-0.89 (m, 2H), 0.63-0.64 (m, 2H)

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-0b85f05c57454247b010abd25029a6b9
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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