Ammonia → 1-(3-Benzyloxy-phenyl)-3-ethoxy-imidazo[1,5-a]pyrazin-8-ylamine

HRID 1992409Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([O:25][CH2:26][CH3:27])[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.[NH3:28]>CC(O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:16]=[C:17]([O:25][CH2:26][CH3:27])[N:18]3[CH:23]=[CH:22][N:21]=[C:20]([NH2:28])[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

Conditions

Temperature: 110 °C

Procedure

A solution of 1-(3-benzyloxy-phenyl)-8-chloro-3-ethoxy-imidazo[1,5-a]pyrazine (20.0 mg, 0.05 mmol) in i-PrOH (5 mL) was saturated with NH3 at −20° C. and heated in a Parr pressure vessel to 110° C. for 72 h. The reaction was concentrated in vacuo, partitioned between DCM and H2O and separated. The aqueous layer was washed with DCM (3×) and the combined organic layers were washed with brine (1×), dried over Na2SO4, filtered and concentrated in vacuo and purified by chromatography on silica gel [eluting with 2% EtOAc in DCM] to yield the desired product as an off-white solid; 1H NMR (CDCl3, 400 MHz) δ 1.45 (t, J=7.2 Hz, 3H), 4.58 (q, J=7.2 Hz, 2H), 4.91 (brs, 2H), 5.10 (s, 2H), 6.86 (d, J=4.8 Hz, 1H), 6.95-6.99 (m, 1H), 7.04 (d, J=5.2 Hz, 1H), 7.17-7.21 (m, 2H), 7.26-7.43 (m, 7H); MS (ES+): m/z=361.19 (100) [MH+], HPLC: tR=2.36 min (MicromassZQ, polar—5 min).

Workup

concentrationThe reaction was concentrated in vacuo
custompartitioned between DCM and H2O
customseparated
washThe aqueous layer was washed with DCM (3×)
washthe combined organic layers were washed with brine (1×)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
custompurified by chromatography on silica gel [eluting with 2% EtOAc in DCM]

Sources & evidence

ORD record: ord-4c43e69029814495b11d521d96bd746d
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07648987B2

Reaction notes

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