Ammonia → {3-[8-Amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol

HRID 2373881Notes

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

Participants

Conditions

Temperature: 110 °C

Procedure

A solution of {3-[1-(3-benzyloxyphenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol (40 mg, 0.095 mmol) in 5 mL of 2N NH3/iPrOH was cooled to −78° C. and charged with NH3 gas for 1 min. This sealed tube was equipped with a teflon O-ring, sealed and heated at 110° C. overnight. The mixture was cooled to rt and the cap was removed. The solution was concentrated under reduced pressure and the crude material was purified by silica gel column chromatography (eluting with 100% ethyl acetate→EtOAc:iPrOH=80:20), yielding the title compound as a white solid, a mixture of cis and trans isomers. MS (ES, Pos.): m/z 401 [MH+]. 1H NMR (CDCl3, 400 MHz) δ 2.37-2.44 (m, 2H), 2.61-2.74 (m, 3H), 3.65-3.82 (m, 3H), 5.03 (br s, 2H, NH2), 5.14 (s, 2H), 7.01-7.46 (m, 11H).

Workup

customsealed
temperatureThe mixture was cooled to rt
customthe cap was removed
concentrationThe solution was concentrated under reduced pressure
customthe crude material was purified by silica gel column chromatography (eluting with 100% ethyl acetate→EtOAc:iPrOH=80:20)

Sources & evidence

ORD record: ord-5742988a813b47afb26499129d2d808a
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07459554B2

Reaction notes

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