Isopropanol → HCID 54596721, compound

HRID 1918811Notes

Reaction equation

HRID 1918811 reaction equation
C([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:24][CH2:23][N:15]3[C:16]4[CH2:17][CH2:18][CH2:19][CH2:20][C:21]=4[CH:22]=[C:14]3[C:13]2=[O:25])=[CH:10][CH:9]=[CH:8][C:7]=1[C:26]1[CH:31]=[C:30]([NH:32][C:33]2[CH:44]=[C:36]3[CH2:37][N:38]([C:41](=[O:43])[CH3:42])[CH2:39][CH2:40][N:35]3[N:34]=2)[C:29](=[O:45])[N:28]([CH3:46])[CH:27]=1)(=O)C.[OH-].[Li+].C1COCC1.CC(O)C>CO.CCOCC.O.CCOC(C)=O>[C:41]([N:38]1[CH2:39][CH2:40][N:35]2[N:34]=[C:33]([NH:32][C:30]3[C:29](=[O:45])[N:28]([CH3:46])[CH:27]=[C:26]([C:7]4[C:6]([CH2:5][OH:4])=[C:11]([N:12]5[CH2:24][CH2:23][N:15]6[C:16]7[CH2:17][CH2:18][CH2:19][CH2:20][C:21]=7[CH:22]=[C:14]6[C:13]5=[O:25])[CH:10]=[CH:9][CH:8]=4)[CH:31]=3)[CH:44]=[C:36]2[CH2:37]1)(=[O:43])[CH3:42]

Participants

9

Reactant 4

HCID 3776IsopropanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 67016178HCID 67016178, compound

Product 1

HCID 54596721HCID 54596721, compoundYield 63%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 25 mL round bottom flask with a magnetic stirrer was charged with 2-(5-(5-acetyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate 108e (69 mg, 0.11 mmol), lithium hydroxide (8 mg, 0.3 mmol), THF (1 mL), i-PrOH (1 mL) and water (2 mL). The mixture stirred at rt for 2 h. After this time, EtOAc (3 mL) and water (3 mL) were added. The separated aqueous layer was extracted with EtOAc (2×5 mL). The combined organics were washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography eluting with a gradient of CH2Cl2-75:18:7 CH2Cl2:Et2O:MeOH to afford a 63% yield (40 mg) of 2-(3-(5-(5-acetyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(hydroxymethyl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one 108. MS (ESI+) m/z 582.3 (M+H).

Workup

  1. extractionThe separated aqueous layer was extracted with EtOAc (2×5 mL)
  2. washThe combined organics were washed with brine (10 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by column chromatography
  7. washeluting with a gradient of CH2Cl2-75:18:7 CH2Cl2

Sources & evidence

ORD record
ord-1eb614a39559467aaf2dd605f1d9fbdd
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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