Water → 2-(3-(Hydroxymethyl)-4-(1-methyl-5-(5-methyl-1H-pyrazol-3-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one

HRID 592583Notes

Reaction equation

HRID 592583 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:14]=[C:13]([CH3:15])[NH:12][N:11]=2)=[CH:5][C:4]([C:16]2[C:21]([CH:22]=[O:23])=[C:20]([N:24]3[CH2:36][CH2:35][N:27]4[C:28]5[CH2:29][CH2:30][CH2:31][CH2:32][C:33]=5[CH:34]=[C:26]4[C:25]3=[O:37])[N:19]=[CH:18][CH:17]=2)=[CH:3]1.O.[Li+].[OH-]>C1COCC1>[OH:23][CH2:22][C:21]1[C:20]([N:24]2[CH2:36][CH2:35][N:27]3[C:28]4[CH2:29][CH2:30][CH2:31][CH2:32][C:33]=4[CH:34]=[C:26]3[C:25]2=[O:37])=[N:19][CH:18]=[CH:17][C:16]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10]2[CH:14]=[C:13]([CH3:15])[NH:12][N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1

Participants

5

Reactant 3

HCID 962Water2×HCID 3939Lithium HydroxideHCID 866841994-(1-Methyl-5-(5-methyl-1H-pyrazol-3-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)nicotinaldehyde

Product 1

HCID 715591562-(3-(Hydroxymethyl)-4-(1-methyl-5-(5-methyl-1H-pyrazol-3-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-oneYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 100-mL single-neck round-bottomed flask was charged with 115b (190 mg, 0.35 mol) in THF/iPA/H2O (5 mL/5 mL/2 mL) and LiOH (85 mg, 3.5 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 115 as a white solid (48 mg, 30% yield). LCMS: [M+H]+ 500. 1H NMR (500 MHz, CDCl3) δ 8.44 (d, J=6.0, 1H), 7.95 (s, 1H), 7.69 (s, 1H), 7.44 (s, 1H), 7.30 (d, J=6.0, 2H), 6.87 (s, 1H), 5.74 (s, 1H), 4.59-3.86 (m, 7H), 3.69 (s, 3H), 2.57-2.56 (m, 4H), 2.25 (s, 3H) 1.88-1.77 (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-f278d90d457044d7b55c199a55358e27
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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