1-((3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)methyl)-3-(4-(tert-butyl)phenyl)urea → 1-((3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(methyl)amino)cyclobutyl)methyl)-3-(4-(tert-butyl)phenyl)urea

HRID 511587ノート

反応式

HRID 511587 の反応式
[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[C@@H:15]2[O:16]C(C)(C)[O:18][C@@H:14]2[C@@H:13]([CH2:21][N:22]([CH3:42])[CH:23]2[CH2:26][CH:25]([CH2:27][NH:28][C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:34][CH:33]=3)=[O:30])[CH2:24]2)[O:12]1>Cl.CO>[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@@H:11]1[O:12][C@H:13]([CH2:21][N:22]([CH3:42])[CH:23]2[CH2:26][CH:25]([CH2:27][NH:28][C:29]([NH:31][C:32]3[CH:33]=[CH:34][C:35]([C:38]([CH3:41])([CH3:39])[CH3:40])=[CH:36][CH:37]=3)=[O:30])[CH2:24]2)[C@@H:14]([OH:18])[C@H:15]1[OH:16]

参加物

3

反応物 1

HCID 677761471-((3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)methyl)-3-(4-(tert-butyl)phenyl)urea

生成物 1

HCID 677746111-((3-((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(methyl)amino)cyclobutyl)methyl)-3-(4-(tert-butyl)phenyl)urea収率 25%

試薬・触媒・溶媒 1

HCID 21893726Hydrochloride methanol溶媒

実験手順

A solution of 1-((3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)methyl)-3-(4-(tert-butyl)phenyl)urea (55 mg) in HCl/MeOH (2.5 mol/L) (2 mL) was stirred at RT for 2 h and then concentrated to dryness. K2CO3 (52 mg) in water (0.5 mL) and MeOH (5 mL) was added. The resulting mixture was stirred for another 10 min at RT, filtered and the filtrate was concentrated. The residue was purified by preparative-HPLC to give Compound 110 (10 mg, yield: 25%) as a white solid. 1HNMR (500 MHz, MeOD): δH 8.26 (s, 1H), 8.18 (s, 1H), 7.26-7.19 (m, 4H), 5.96 (d, J=4.5 Hz, 1H), 4.674-4.655 (m, 1H), 4.24-4.16 (m, 2H), 3.15 (d, J=5.0 Hz, 2H), 2.83-2.73 (m, 3H), 2.20-1.59 (m, 8H), 1.26 (s, 9H) ppm; ESI-MS (m/z): 539.3 [M+1]+.

後処理

  1. concentrationconcentrated to dryness
  2. additionK2CO3 (52 mg) in water (0.5 mL) and MeOH (5 mL) was added
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated
  5. customThe residue was purified by preparative-HPLC

出典と根拠

ORDレコード
ord-ce00406e852d400ba972c9de406170dc
出典データセット
uspto-grants-2015_08
特許番号
US09096634B2

反応ノート

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