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

HRID 2373881ノート

反応式

HRID 2373881 の反応式
[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

参加物

4

反応物 2

HCID 222AmmoniaHCID 59852798{3-[1-(3-Benzyloxyphenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol

生成物 1

HCID 11406927{3-[8-Amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol

試薬・触媒・溶媒 1

HCID 183319422-Propanol, reaction products with ammonia, distn. residues溶媒

反応条件

温度
110 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-5742988a813b47afb26499129d2d808a
出典データセット
uspto-grants-2008_12
特許番号
US07459554B2

反応ノート

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