Ammonia → 1-{4-[3-(8-Amino-1-iodoimidazo[1,5-a]pyrazin-3-yl)cyclobutyl]piperazin-1-yl}ethanone

HRID 1163220Notes

Reaction equation

Cl[C:2]1[C:3]2[N:4]([C:8]([CH:12]3[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][N:19]([C:22](=[O:24])[CH3:23])[CH2:18][CH2:17]4)[CH2:13]3)=[N:9][C:10]=2[I:11])[CH:5]=[CH:6][N:7]=1.[NH3:25]>C(O)(C)C>[NH2:25][C:2]1[C:3]2[N:4]([C:8]([CH:12]3[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][N:19]([C:22](=[O:24])[CH3:23])[CH2:18][CH2:17]4)[CH2:13]3)=[N:9][C:10]=2[I:11])[CH:5]=[CH:6][N:7]=1

Participants

Conditions

Temperature: 110 °C

Procedure

1-{4-[3-(8-Chloro-1-iodo-imidazo[1,5-a]pyrazin-3-yl)-cyclobutyl]-piperazin-1-yl}-ethanone (13.2 g, 0.029 mol) was dissolved in isopropyl alcohol (100 mL) into a Parr pressure reactor. The vessel was cooled to −78° C. and saturated with ammonia gas and sealed. The reaction was heated for 19 h at 110° C., at which point the reaction was cooled and the solvent concentrated in vacuo. The crude product was purified via silica gel chromatography eluting with 5-10% MeOH (7M NH3): CH2Cl2 to yield the title compounds as an off white solid; MS (ES+): m/z 440.89 (100) [MH+], 441.89 (20) [MH++]; HPLC: tR=0.46 min (OpenLynx, polar—5 min); 1H NMR (CDCl3, 400 MHz) δ 2.09 (s, 3H) 2.28-2.48 (m, 6H) 2.54-2.71 (m, 2H) 2.80-2.99 (m, 1H) 3.27-3.43 (m, 1H) 3.43-3.54 (m, 2H) 3.56-3.70 (m, 2H) 7.02 (d, J=5.05 Hz, 1H) 7.16 (d, J=5.05 Hz, 2H).

Workup

customsealed
temperaturewas cooled
concentrationthe solvent concentrated in vacuo
customThe crude product was purified via silica gel chromatography
washeluting with 5-10% MeOH (7M NH3)

Sources & evidence

ORD record: ord-c2941f74ac35487c865a0e921cb66e64
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820662B2

Reaction notes

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