Lithium Hydroxide → 2-[3-(Hydroxymethyl)-4-[1-methyl-5-[[5-(1-methylazetidin-3-yl)-2-pyridyl]amino]-6-oxo-3-pyridyl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-1-one

HRID 1411919Notes

Reaction equation

HRID 1411919 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:32]2[CH2:44][CH2:43][C:42]3[N:41]4[C:36]([CH2:37][CH2:38][CH2:39][CH2:40]4)=[CH:35][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:24]=[CH:23][C:22]([CH:25]3[CH2:28][N:27]([CH3:29])[CH2:26]3)=[CH:21][N:20]=2)[C:15](=[O:30])[N:14]([CH3:31])[CH:13]=1)(=O)C.[OH-].[Li+]>C1COCC1.C(O)(C)C.O>[OH:4][CH2:5][C:6]1[C:7]([N:32]2[CH2:44][CH2:43][C:42]3[N:41]4[C:36]([CH2:37][CH2:38][CH2:39][CH2:40]4)=[CH:35][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:24]=[CH:23][C:22]([CH:25]3[CH2:28][N:27]([CH3:29])[CH2:26]3)=[CH:21][N:20]=2)[C:15](=[O:30])[N:14]([CH3:31])[CH:13]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86684465(4-(1-Methyl-5-(5-(1-methylazetidin-3-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)pyridin-3-yl)methyl Acetate

Product 1

HCID 866844662-[3-(Hydroxymethyl)-4-[1-methyl-5-[[5-(1-methylazetidin-3-yl)-2-pyridyl]amino]-6-oxo-3-pyridyl]-2-pyridyl]-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-1-oneYield 30%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 244d (90 mg, 0.15 mmol) and lithium hydroxide (60 mg, 1.5 mmol) in THF/i-propanol (5:3, 8 mL) and water (2 mL) was stirred at 30° C. for 1 h. The mixture was evaporated in vacuo and the residue was diluted with water (3 mL). It was then extracted with ethyl acetate (20 mL×2). The combined ethyl acetate extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 244 (25 mg, 30%) as white solid. MS-ESI: [M+H]+ 566.4. 1H NMR (500 MHz, CDCl3) δ 8.74 (d, J=2.5 Hz, 1H), 8.51 (d, J=5.5 Hz, 1H), 8.16 (d, J=2.0 Hz, 1H), 7.91 (s, 1H), 7.87 (d, J=2.0 Hz, 1H), 7.59-7.57 (m, 1H), 7.35 (d, J=5.0 Hz, 1H), 6.85-6.83 (m, 1H), 6.33 (s, 1H), 5.04-5.01 (m, 1H), 4.67-4.65 (m, 1H), 4.44-4.39 (m, 1H), 4.33-4.29 (m, 1H), 3.95-3.91 (m, 1H), 3.86-3.83 (m, 2H), 3.76-3.74 (m, 1H), 3.73 (s, 3H), 3.62-3.59 (m, 1H), 3.16-3.13 (m, 2H), 3.02-2.95 (m, 2H), 2.84-2.83 (m, 2H), 2.39 (s, 3H), 2.05-2.02 (m, 2H), 1.90-1.87 (m, 2H).

Workup

  1. customThe mixture was evaporated in vacuo
  2. additionthe residue was diluted with water (3 mL)
  3. extractionIt was then extracted with ethyl acetate (20 mL×2)
  4. extractionThe combined ethyl acetate extract
  5. concentrationwas concentrated under reduced pressure
  6. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-32e17040ee1d426d8d1fc6ca9856bcd5
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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