Water → 2-(4-(5-(5-ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-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 1411691Notes

Reaction equation

HRID 1411691 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:32]2[CH2:44][CH2:43][N:35]3[C:36]4[CH2:37][CH2:38][CH2:39][CH2:40][C:41]=4[CH:42]=[C:34]3[C:33]2=[O:45])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:29]=[C:22]3[CH2:23][N:24]([CH2:27][CH3:28])[CH2:25][CH2:26][N:21]3[N:20]=2)[C:15](=[O:30])[N:14]([CH3:31])[CH:13]=1)(=O)C.O.[OH-].[Li+]>CC(O)C.O1CCCC1>[CH2:27]([N:24]1[CH2:25][CH2:26][N:21]2[N:20]=[C:19]([NH:18][C:16]3[C:15](=[O:30])[N:14]([CH3:31])[CH:13]=[C:12]([C:11]4[CH:10]=[CH:9][N:8]=[C:7]([N:32]5[CH2:44][CH2:43][N:35]6[C:36]7[CH2:37][CH2:38][CH2:39][CH2:40][C:41]=7[CH:42]=[C:34]6[C:33]5=[O:45])[C:6]=4[CH2:5][OH:4])[CH:17]=3)[CH:29]=[C:22]2[CH2:23]1)[CH3:28]

Participants

6

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 86684315(4-(5-(5-Ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-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 866843162-(4-(5-(5-ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-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 28.4%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 177a (300 mg, 0.49 mmol) in propan-2-ol (4 mL), tetrahydrofuran (4 mL), and water (1 mL) was added lithium hydroxide (35 mg, 1.47 mmol). The mixture was stirred at room temperature for 0.5 h. It was evaporated and the residue was purified by reverse-phase prep-HPLC to afford 177 (79 mg, 28%) as a white solid. MS-ESI: [M+H]+ 569. 1H NMR (500 MHz, CDCl3) δ 8.46 (d, J=5.5 Hz, 1H), 7.92 (d, J=2.0 Hz, 1H), 7.70 (d, J=2.0 Hz, 1H), 7.39 (s, 1H), 7.33 (d, J=5.5 Hz, 1H), 6.88 (s, 1H), 5.69 (s, 1H), 4.99-4.97 (m, 1H), 4.61-4.60 (m, 1H), 4.48-4.46 (m, 1H), 4.33-4.31 (m, 1H), 4.14-4.06 (m, 4H), 3.87-3.85 (m, 1H), 3.69 (s, 3H), 3.62 (d, J=5.5 Hz, 2H), 2.91 (d, J=5.0 Hz, 2H), 2.63-2.55 (m, 6H), 1.91-1.87 (m, 2H), 1.79-1.78 (m, 2H), 1.17 (t, J=7.5 Hz, 3H).

Workup

  1. customIt was evaporated
  2. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-4ebb04b833c5457dad1a266aaec592bd
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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