Lithium Hydroxide → 2-[3'-Hydroxymethyl-1-methyl-6-oxo-5-(pyrazin-2-ylamino)-1,6-dihydro-[3,4']bipyridinyl-2'-yl]-7,7-dimethyl-3,4,7,8-tetrahydro-2H,6H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one

HRID 592782Notes

Reaction equation

HRID 592782 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:27]2[CH2:38][CH2:37][N:36]3[C:29](=[CH:30][C:31]4[CH2:32][C:33]([CH3:40])([CH3:39])[CH2:34][C:35]=43)[C:28]2=[O:41])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:24]=[N:23][CH:22]=[CH:21][N:20]=2)[C:15](=[O:25])[N:14]([CH3:26])[CH:13]=1)(=O)C.[OH-].[Li+]>C(O)(C)C.C1COCC1.O>[OH:4][CH2:5][C:6]1[C:7]([N:27]2[CH2:38][CH2:37][N:36]3[C:35]4[CH2:34][C:33]([CH3:39])([CH3:40])[CH2:32][C:31]=4[CH:30]=[C:29]3[C:28]2=[O:41])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:24]=[N:23][CH:22]=[CH:21][N:20]=2)[C:15](=[O:25])[N:14]([CH3:26])[CH:13]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86684339(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{1-methyl-6-oxo-5-[(pyrazin-2-yl)amino]-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl Acetate

Product 1

HCID 715575972-[3'-Hydroxymethyl-1-methyl-6-oxo-5-(pyrazin-2-ylamino)-1,6-dihydro-[3,4']bipyridinyl-2'-yl]-7,7-dimethyl-3,4,7,8-tetrahydro-2H,6H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-oneYield 35%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 188a (150 mg, 0.27 mmol) and lithium hydroxide (103 mg, 2.7 mmol) in i-propanol/THF (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 extracted with ethyl acetate (2×20 mL). The combined ethyl acetate extract was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 188 (40 mg, 35%) as a white solid. MS-ESI: [M+H]+ 512.3. 1H NMR (500 MHz, CHCl3) δ 8.73 (d, J=2.0 Hz, 1H), 8.53 (d, J=5.0 Hz, 1H), 8.29 (s, 1H), 8.15-8.13 (m, overlap, 2H), 8.02-8.00 (m, 2H), 7.38 (d, J=5.0 Hz, 1H), 6.86 (s, 1H), 5.12 (s, 1H), 4.68-4.51 (m, 2H), 4.33-4.29 (m, 1H), 4.18 (t, J=5.5 Hz, 2H), 3.91-3.86 (m, 1H), 3.75 (s, 3H), 2.60-2.58 (m, 2H), 2.53 (s, 2H), 1.28 (s, 6H).

Workup

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

Sources & evidence

ORD record
ord-53c31b78024a49ae84f80a5a59609dd3
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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