Isopropanol → (S)-10-fluoro-2-(5-fluoro-2-(hydroxymethyl)-3-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one

HRID 1026480Notes

Reaction equation

HRID 1026480 reaction equation
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][N:28]([CH:31]5[CH2:34][O:33][CH2:32]5)[CH2:27][C@@H:26]4[CH3:35])=[CH:21][N:20]=3)[C:15](=[O:36])[N:14]([CH3:37])[CH:13]=2)=[CH:10][C:9]([F:38])=[CH:8][C:7]=1[N:39]1[CH2:52][CH2:51][N:42]2[C:43]3[CH2:44][CH2:45][CH2:46][CH2:47][C:48]=3[C:49]([F:50])=[C:41]2[C:40]1=[O:53])(=O)C.[OH-].[Li+].C(O)(C)C.C1COCC1>O>[F:50][C:49]1[C:48]2[CH2:47][CH2:46][CH2:45][CH2:44][C:43]=2[N:42]2[CH2:51][CH2:52][N:39]([C:7]3[CH:8]=[C:9]([F:38])[CH:10]=[C:11]([C:12]4[CH:17]=[C:16]([NH:18][C:19]5[CH:24]=[CH:23][C:22]([N:25]6[CH2:30][CH2:29][N:28]([CH:31]7[CH2:32][O:33][CH2:34]7)[CH2:27][C@@H:26]6[CH3:35])=[CH:21][N:20]=5)[C:15](=[O:36])[N:14]([CH3:37])[CH:13]=4)[C:6]=3[CH2:5][OH:4])[C:40](=[O:53])[C:41]=12

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 86683749(S)-4-Fluoro-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)benzyl Acetate

Product 1

HCID 71525349(S)-10-fluoro-2-(5-fluoro-2-(hydroxymethyl)-3-(1-methyl-5-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-oneYield 51%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with 119d (90 mg, 1.0 eq., 0.12 mmol), lithium hydroxide (9.0 mg, 3.0 eq., 0.37 mmol), i-propanol (3 mL), THF (3 mL), and water (2 mL). The mixture was stirred at room temperature for 1 h. It was then filtered and concentrated. The residue was purified by reverse-phase prep-HPLC to afford 119 (42 mg, 49%). MS: [M+H]+ 686.3. 1H NMR (500 MHz, CDCl3) δ 8.54 (dd, J=2.0 Hz, 9.0, 1H), 7.94-7.93 (m, 1H), 7.81 (d, J=4.0 Hz, 1H), 7.45-7.44 (m, 1H), 7.31 (dd, J=3.0, 9.0 Hz, 1H), 7.15-7.14 (m, 1H), 6.94 (dd, J=2.0, 9.0 Hz, 1H), 6.81 (d, J=8.5 Hz, 1H), 4.71-4.61 (m, 4H), 4.53 (d, J=9.5 Hz, 1H), 4.32-4.31 (m, 2H), 4.15-4.08 (m, 3H), 3.89-3.86 (m, 1H), 3.69 (s, 3H), 3.55-3.43 (m, 2H), 3.07 (m, 2H), 2.57-2.46 (m, 7H), 2.20-2.16 (m, 1H), 1.88-1.76 (m, 4H), 0.98-096 (m, 3H).

Workup

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. filtrationIt was then filtered
  3. concentrationconcentrated
  4. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-cadbc4c95fb94322b5500535b2b87cb7
Source dataset
uspto-grants-2014_05
Patent number
US08729072B2

Reaction notes

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