Methanol → Methyl 4-(3-amino-6-(4-(hydroxymethyl)cyclohexyl)pyrazin-2-yl)-2-fluorobenzoate

HRID 596116Notes

Reaction equation

HRID 596116 reaction equation
[NH2:1][C:2]1[C:3]([C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]([F:33])[CH:24]=2)=[N:4][C:5]([C:8]2[CH2:13][CH2:12][CH:11]([CH2:14][O:15]CC3C=CC=CC=3)[CH2:10][CH:9]=2)=[CH:6][N:7]=1.CO>C1COCC1.[Pd]>[NH2:1][C:2]1[C:3]([C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]([F:33])[CH:24]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][CH:11]([CH2:14][OH:15])[CH2:10][CH2:9]2)=[CH:6][N:7]=1

Participants

5

Reactant 2

HCID 887MethanolHCID 118046409Methyl 4-(3-amino-6-(4-((benzyloxy)methyl)cyclohex-1-en-1-yl)pyrazin-2-yl)-2-fluorobenzoate

Product 1

HCID 118045488Methyl 4-(3-amino-6-(4-(hydroxymethyl)cyclohexyl)pyrazin-2-yl)-2-fluorobenzoateYield 70.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 4-(3-amino-6-(4-((benzyloxy)methyl)cyclohex-1-en-1-yl)pyrazin-2-yl)-2-fluorobenzoate (381 mg, 0.851 mmol) was dissolved in THF (5 mL) and then MeOH (15 mL) was added and then Pd—C (10% wet) (550 mg, 0.517 mmol) was added. The mixture was put under vacuum and purged with hydrogen and this cycle was repeated thrice and then finally under hydrogen overnight. After 14 h, LCMS indicated alkene saturation but only partial benzyl deprotection, and therefore another Pd—C (10% wet) (700 mg) was added and the mixture stirred at room temperature for another 5 h after which complete benzyl deprotection observed. The reaction mixture was filtered and concentrated in vacuo to afford 215.6 mg of the desired product as a mixture of diasteromers (cis/trans unspecified) (70%). LCMS (m/z): 360.2 (MH+), 0.71, 0.72 min.

Workup

  1. custompurged with hydrogen
  2. customfinally under hydrogen overnight
  3. additionanother Pd—C (10% wet) (700 mg) was added
  4. filtrationThe reaction mixture was filtered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-369f7fa89e8d4a5689281315ecefb22e
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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