Sodium 2-methylbutan-2-olate → 1-(3-Benzyloxy-phenyl)-3-(3-methoxymethylene-cyclobutyl)-imidazo[1,5-a]pyrazin-8-ylamine

HRID 2373914Notes

Reaction equation

HRID 2373914 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([CH:25]3[CH2:28][C:27](=[CH:29][O:30][CH3:31])[CH2:26]3)[N:18]3[CH:23]=[CH:22][N:21]=[C:20](Cl)[C:19]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCC([O-])(C)C.[Na+].C(OC1C=C(C2[N:54]=C(C3CC(=O)C3)N3C=CN=C(Cl)C=23)C=CC=1)C1C=CC=CC=1>C1C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([CH:25]3[CH2:28][C:27](=[CH:29][O:30][CH3:31])[CH2:26]3)[N:18]3[CH:23]=[CH:22][N:21]=[C:20]([NH2:54])[C:19]=23)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 2733478Sodium 2-methylbutan-2-olateHCID 598527371-(3-Benzyloxy-phenyl)-8-chloro-3-(3-methoxymethylene-cyclobutyl)-imidazo[1,5-a]pyrazineHCID 598528193-{1-[3-(Benzyloxy)phenyl]-8-chloroimidazo[1,5-a]pyrazin-3-yl}cyclobutanone

Product 1

HCID 111541581-(3-Benzyloxy-phenyl)-3-(3-methoxymethylene-cyclobutyl)-imidazo[1,5-a]pyrazin-8-ylamine

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent3×

Conditions

Temperature
70 °C

Procedure

1-(3-Benzyloxy-phenyl)-8-chloro-3-(3-methoxymethylene-cyclobutyl)-imidazo[1,5-a]pyrazine: To a solution of Ph3PCH2OMeCl (2.6 g, 7.44 mmol) in benzene (37 mL) a solution of sodium tert-amylate (819.0 mg, 7.44 mmol) in benzene (9.0 mL) was added at rt. The dark red solution was allowed to stir at rt for 10 min. at which point a solution of 3-[1-(3-Benzyloxy-phenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]-cyclobutanone in benzene (30.0 mL) was added dropwise at rt. The reaction mixture was then heated to 70° C. for 4 h. The reaction was then quenched with NH4Cl sat. Aq. and extracted with diethyl ether (3×). The organic layers were washed with H2O (1×), brine (1×), dried over Na2SO4, filtered and concentrated in vacuo. Purification via HPFC using a 50 g Jones silica gel column (30% EtOAc:Hex) to yield the desired product as a light yellow solid; 1H NMR (CDCl3, 400 MHz) δ 3.29-3.33 (m, 4H), 3.59 (s, 3H), 3.90 (q, 1H, J=8.2 Hz), 5.14 (s, 2H), 5.93 (s, 1H), 7.26-7.66 (m, 11H); MS (ES) 432.05 (M+1), 434.01 (M+3), 435.02 (M+4).

Workup

  1. additionwas added dropwise at rt
  2. customThe reaction was then quenched with NH4Cl sat. Aq.
  3. extractionextracted with diethyl ether (3×)
  4. washThe organic layers were washed with H2O (1×), brine (1×)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification via HPFC

Sources & evidence

ORD record
ord-32cb7cf1810f4d898685535e26c904ee
Source dataset
uspto-grants-2008_12
Patent number
US07459554B2

Reaction notes

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