Tetrahydrofuran → HCID 178508463, compound

HRID 244087Notes

Reaction equation

HRID 244087 reaction equation
C1COCC1.C[O:7][C:8]([C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16]2[N:20]3[CH:21]=[CH:22][N:23]=[C:24]([NH2:25])[C:19]3=[C:18]([C:26]3[CH:35]=[C:34]4[C:29]([CH:30]=[CH:31][C:32]([C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)=[N:33]4)=[CH:28][CH:27]=3)[N:17]=2)[CH2:12][CH2:11]1)=[O:9].[OH-].[Na+]>CO>[NH2:25][C:24]1[C:19]2[N:20]([C:16]([C@H:13]3[CH2:12][CH2:11][C@H:10]([C:8]([OH:9])=[O:7])[CH2:15][CH2:14]3)=[N:17][C:18]=2[C:26]2[CH:35]=[C:34]3[C:29]([CH:30]=[CH:31][C:32]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[N:33]3)=[CH:28][CH:27]=2)[CH:21]=[CH:22][N:23]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 178501047HCID 178501047, compound

Product 1

HCID 178508463HCID 178508463, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A THF solution (2 mL) of trans-4-[8-amino-1-(2-phenylquinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methyl ester was charged with 10M NaOH (0.31 mL, 3.1 mmol); a minimal amount of methanol was added to homogenize the reaction mixture. The reaction stirred at rt for 2 h. The reaction mixture was concentrated to solids and acidified to pH 5 with 2 MHCl. The aqueous layer was extracted with CHCl3 (5×) and combined organic layers were dried over Na2SO4, filtered, and concentrated to the desired compound as a orange solid; 1H NMR (CDCl3, 400 MHz) δ 1.62-1.73 (m, 2H), 1.92-2.02 (m, 2H), 2.15-2.27 (m, 4H), 2.44-2.60 (m, 1H), 2.99-3.08 (m, 1H), 3.72 (s, 3H), 5.25 (s, 2H), 6.91 (d, 1H, J=6.0 Hz), 7.29-7.33 (m, 1H), 7.51-7.59 (m, 3H), 7.81 (dd, 1H, J=2.0 Hz, 8.4 Hz), 8.00-8.05 (m, 2H), 8.21-8.23 (m, 2H), 8.32 (d, 1H, J=9.2 Hz), 8.41-8.42 (m, 1H); MS (ES+): m/z 464.0 [MH+]; HPLC: tR=2.3 min (Micromass Platform II, polar—5 min).

Workup

  1. stirringThe reaction stirred at rt for 2 h
  2. concentrationThe reaction mixture was concentrated to solids
  3. extractionThe aqueous layer was extracted with CHCl3 (5×)
  4. dry with materialwere dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to the desired compound as a orange solid
  7. customHPLC: tR=2.3 min (Micromass Platform II, polar—5 min)

Sources & evidence

ORD record
ord-a56263afe35948b1bcfe07891a71ecec
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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