Ammonia → (3-[8-Amino-1-(2-phenylquinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-cyclobutyl)-methanol

HRID 1028755Notes

Reaction equation

HRID 1028755 reaction equation
Cl[C:2]1[C:3]2[N:4]([C:8]([CH:27]3[CH2:30][CH:29]([CH2:31][OH:32])[CH2:28]3)=[N:9][C:10]=2[C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[CH:16][C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1.[NH3:33]>CC(O)C>[NH2:33][C:2]1[C:3]2[N:4]([C:8]([CH:27]3[CH2:30][CH:29]([CH2:31][OH:32])[CH2:28]3)=[N:9][C:10]=2[C:11]2[CH:20]=[C:19]3[C:14]([CH:15]=[CH:16][C:17]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 57681056{3-[8-Chloro-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol

Product 1

HCID 11510031(3-[8-Amino-1-(2-phenylquinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-cyclobutyl)-methanol

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
110 °C

Procedure

A solution of {3-[8-chloro-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-cyclobutyl}-methanol (compound of Formula II-B where Z=cyclobutyl and Q1=2-phenylquinolin-7-yl) (265 mg, 0.6 mmol) in 5 mL of 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. for 3 days. The mixture was cooled to −78° C. and the cap was removed. The salt was filtered off and the filtrate was concentrated under reduced pressure. The crude material was purified by silica gel column chromatography (eluting with 100% ethyl acetate→EtOAc:MeOH=90:10) to obtain the title compound as a light yellow solid, a mixture of cis and trans isomers in the ratio of 5:1; MS (ES+): m/z 422 [MH+]; 1H NMR (CDCl3, 400 MHz): δ=2.42-2.48 (m, 2H), 2.66-2.74 (m, 3H), 3.71-3.85 (m, 3H), 5.25 (br s, 2H), 7.10-7.19 (m, 2H), 7.46-7.57 (m, 3H), 7.91-7.97 (m, 3H), 8.18-8.21 (m, 2H), 8.27 (d, J=8.6 Hz, 1H), 8.42, 8.44 (2×s, 1H, 5:1 ratio).

Workup

  1. customsealed
  2. temperatureThe mixture was cooled to −78° C.
  3. customthe cap was removed
  4. filtrationThe salt was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe crude material was purified by silica gel column chromatography (eluting with 100% ethyl acetate→EtOAc:MeOH=90:10)

Sources & evidence

ORD record
ord-73e7e0d9d7274edc96b9d4ccb568c589
Source dataset
uspto-grants-2014_05
Patent number
US08735405B2

Reaction notes

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