Ammonia → HCID 11486769, compound

HRID 2373909Notes

Reaction equation

C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]3[N:19]=[C:20]([CH:28]4[CH2:31][CH2:30][CH2:29]4)[N:21]4[CH:26]=[CH:25][N:24]=[C:23]([NH2:27])[C:22]=34)[CH:13]=2)[CH:5]=1.[NH3:33]>CO>[NH2:27][C:23]1[C:22]2[N:21]([C:20]([CH:28]3[CH2:31][CH2:30][CH2:29]3)=[N:19][C:18]=2[C:14]2[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=2)[O:11][CH2:10][C:6]2[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=2)[C:3]([NH2:33])=[O:2])[CH:26]=[CH:25][N:24]=1

Participants

Conditions

Temperature: 60 °C

Procedure

3-[3-(8-Amino-3-cyclobutyl-imidazo[1,5-a]pyrazin-1-yl)-phenoxymethyl]-benzoic acid methyl ester (150 mg, 0.35 mmol) was dissolved in a sealed tube with 2.0 ml of 7N NH3 in MeOH and heated to 60° C. overnight. LC/MS analysis indicated that the reaction was incomplete, therefore NH3 gas was bubbled into the solution and the reaction was run at 100° C. in a 100 mL Parr pressure vessel. The product was chromatographed on silica gel [Jones Flashmaster, 5 g cartridge, eluting with 2% NH3 in MeOH:CH2Cl2] to yield the title compound as a white solid; 1H NMR (CDCl3, 400 MHz) δ 1.99-2.08 (m, 1H), 2.13-2.25 (m, 1H), 2.46-2.55 (m, 2H), 2.55-2.65 (m, 2H), 3.78-3.87 (m, 1H), 5.21 (s, 2H), 6.95 (d, J=5.2 Hz, 1H), 7.08-7.11 (m, 1H), 7.13 (d, J=5.6 Hz, 1H), 7.22-7.24 (m, 2H), 7.42-7.51 (m, 2H), 7.61 (d, J=8.4 Hz, 1H), 7.80-7.83 (m, 1H), 7.94 s, 1H); MS (ES+): m/z 414.21 (100) [MH+].

Workup

customNH3 gas was bubbled into the solution
customwas run at 100° C. in a 100 mL Parr pressure vessel
customThe product was chromatographed on silica gel [Jones Flashmaster, 5 g cartridge, eluting with 2% NH3 in MeOH:CH2Cl2]

Sources & evidence

ORD record: ord-e973a312384242cda240fdc5a4b3848b
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07459554B2

Reaction notes

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