Pyridine → Toluene-4-sulfonic acid 3-[8-amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutylmethyl ester

HRID 2373880ノート

反応式

HRID 2373880 の反応式
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:25]3[CH2:28][CH:27]([CH2:29][OH:30])[CH2:26]3)=[N:9][C:10]=2[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:12]=2)[CH:5]=[CH:6][N:7]=1.N1C=CC=CC=1.[O:37](S(C1C=CC(C)=CC=1)(=O)=O)[S:38]([C:41]1[CH:47]=[CH:46][C:44]([CH3:45])=[CH:43][CH:42]=1)(=O)=[O:39]>C(Cl)Cl>[NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:25]3[CH2:28][CH:27]([CH2:29][O:30][S:38]([C:41]4[CH:47]=[CH:46][C:44]([CH3:45])=[CH:43][CH:42]=4)(=[O:39])=[O:37])[CH2:26]3)=[N:9][C:10]=2[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:12]=2)[CH:5]=[CH:6][N:7]=1

参加物

5

反応物 3

HCID 1049PyridineHCID 77773Toluene-p-sulphonic anhydrideHCID 11406927{3-[8-Amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol

生成物 1

HCID 11215034Toluene-4-sulfonic acid 3-[8-amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutylmethyl ester

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A solution of {3-[8-amino-1-(3-benzyloxyphenyl)-imidazo[1,5-a]pyrazin-3-yl]cyclobutyl}methanol (23 mg, 0.057 mmol) in dry methylene chloride (3 mL) was charged with pyridine (0.1 mL) and Ts2O (21 mg, 0.063 mmol) at −20° C. under N2 atmosphere. The mixture was slowly warmed to rt overnight. The reaction was quenched with water (1 mL), diluted with ethyl acetate (20 mL), washed with sat. aq. NaHCO3 (10 mL) and brine (2×10 mL), and dried over anhydrous sodium sulfate. The filtrate was concentrated under reduced pressure, and the crude material was purified by silica gel column chromatography (eluting with EtOAc:MeOH=98:2→96:4), yielding the title compound as a white solid. Partial trans isomer was removed by chromatography and the ratio of cis and trans isomers raised to 8:1; MS (ES, Pos.): m/z 555 [MH+]. 1H NMR (CDCl3, 400 MHz) δ 2.27-2.35 (m, 2H), 2.41 (s, 3H), 2.55-2.62 (m, 2H), 2.80 (m, 1H), 3.66 (m, 1H), 4.07 (d, J=6.7 Hz, 2H), 5.01 (br s, 2H, NH2), 5.15 (s, 2H), 7.02-7.85 (m, 15H). Anal. Calcd for C31H30N4O4S.1/3H2O: C, 66.41; H, 5.51; N, 9.99. Found: C, 66.43; H, 5.44; N, 10.07.

後処理

  1. customThe reaction was quenched with water (1 mL)
  2. additiondiluted with ethyl acetate (20 mL)
  3. washwashed with sat. aq. NaHCO3 (10 mL) and brine (2×10 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe crude material was purified by silica gel column chromatography (eluting with EtOAc:MeOH=98:2→96:4)

出典と根拠

ORDレコード
ord-ba9a4a75a20a4885b0f17d85bce88354
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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