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

HRID 592592Notes

Reaction equation

HRID 592592 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:31]2[CH2:43][CH2:42][N:34]3[C:35]4[CH2:36][CH2:37][CH2:38][CH2:39][C:40]=4[CH:41]=[C:33]3[C:32]2=[O:44])=[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]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][N:20]=2)[C:15](=[O:29])[N:14]([CH3:30])[CH:13]=1)(=O)C.O.[Li+].[OH-]>C1COCC1>[OH:4][CH2:5][C:6]1[C:7]([N:31]2[CH2:43][CH2:42][N:34]3[C:35]4[CH2:36][CH2:37][CH2:38][CH2:39][C:40]=4[CH:41]=[C:33]3[C:32]2=[O:44])=[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]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][N:20]=2)[C:15](=[O:29])[N:14]([CH3:30])[CH:13]=1

Participants

5

Reactant 3

HCID 962Water2×HCID 3939Lithium HydroxideHCID 86684204(4-(1-Methyl-5-(5-(methylsulfonyl)pyridin-2-ylamino)-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 715592972-(3-(hydroxymethyl)-4-(1-methyl-5-(5-(methylsulfonyl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)-3,4,6,7,8,9-hexahydro-pyrazino[1,2-a]indol-1(2H)-oneYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 100-mL single-neck round-bottomed flask compound was charged with 117e (100 mg, 0.2 mol) in THF/iPA/H2O (5 mL/5 mL/2 mL) and LiOH (50 mg, 2 mmol) while stirring. This mixture was stirred at 50° C. for 0.5 h. Then 20 mL H2O was added and the mixture was extracted with EA (30 mL×3). The combined organic layer was dried over Na2SO4 and concentrated to give a yellow solid, which was further purified by reverse-phase prep-HPLC to afford 117 as a white solid (72 mg, 90% yield). MS: [M+H]+ 575. 1H NMR (500 MHz, CDCl3) δ 9.39 (s, 1H), 8.84 (d, J=2.0, 1H), 8.60 (d, J=2.5, 1H), 8.50 (d, J=2.5, 1H), 7.98 (dd, J=2.5, 4.0, 1H), 7.69 (d, J=2.4, 1H), 7.49-7.47 (d, J=9.0, 1H), 7.38-7.37 (m, 1H), 6.58 (s, 1H), 4.99 (t, J=4.5, 1H), 4.47-4.39 (m, 2H), 4.26-4.11 (m, 3H), 3.88-3.86 (m, 1H), 3.62 (s, 3H), 3.19 (s, 3H), 2.66-2.54 (m, 2H), 2.48-2.46 (m, 2H), 1.79-1.66 (m, 4H)

Workup

  1. stirringThis mixture was stirred at 50° C. for 0.5 h
  2. extractionthe mixture was extracted with EA (30 mL×3)
  3. dry with materialThe combined organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customto give a yellow solid, which
  6. customwas further purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-340e869bac61494b910272c129d260a6
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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