Ammonia → 3-(8-Amino-1-iodoimidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutanol

HRID 1878845Notes

Reaction equation

[NH3:1].Cl[C:3]1[C:4]2[N:5]([C:9]([CH:13]3[CH2:16][C:15]([CH3:18])([OH:17])[CH2:14]3)=[N:10][C:11]=2[I:12])[CH:6]=[CH:7][N:8]=1>C(O)(C)C.C1COCC1>[NH2:1][C:3]1[C:4]2[N:5]([C:9]([CH:13]3[CH2:16][C:15]([CH3:18])([OH:17])[CH2:14]3)=[N:10][C:11]=2[I:12])[CH:6]=[CH:7][N:8]=1

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of 2M ammonia in isopropanol (80 mL) and THF (5 mL) was added to 3-(8-chloro-1-iodoimidazo[1,5-α]pyrazin-3-yl)-1-methylcyclobutanol (2.77 g, 7.62 mmol) in a Parr pressure reactor. The mixture was cooled to at −78° C. then ammonia gas was bubbled into the solution for 4-6 min. The reactor was sealed then heated at 110° C. for 15 h. The solvent was then removed in vacuo and the residue purified by chromatography over silica gel eluting with 7% MeOH in DCM to afford desired product. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.44 (s, 3 H), 2.32-2.51 (m, 4 H), 3.33-3.52 (m, 1 H), 6.61 (br.s., 2 H), 7.03 (d, J=5.05 Hz, 1 H) and 7.62 (d, J=5.05 Hz, 1 H).

Workup

customammonia gas was bubbled into the solution for 4-6 min
customThe reactor was sealed
temperaturethen heated at 110° C. for 15 h
customThe solvent was then removed in vacuo
customthe residue purified by chromatography over silica gel eluting with 7% MeOH in DCM

Sources & evidence

ORD record: ord-4951460c488f41c99278b5e8bfe388b6
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08314111B2

Reaction notes

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