Tetrahydrofuran → tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-hydroxy-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate

HRID 447618ノート

反応式

HRID 447618 の反応式
[NH2:1][S:2]([N:5]([CH2:13][C@@H:14]1[CH2:18][C@@H:17]([O:19][C:20]2[CH:25]=[C:24]([NH:26][C@@H:27]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH3:37])[N:23]=[CH:22][N:21]=2)[CH2:16][C@@H:15]1[O:38][Si](C(C)(C)C)(C)C)[C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])(=[O:4])=[O:3].C1COCC1.F.N1C=CC=CC=1>N1C=CC=CC=1>[NH2:1][S:2]([N:5]([CH2:13][C@@H:14]1[CH2:18][C@@H:17]([O:19][C:20]2[CH:25]=[C:24]([NH:26][C@@H:27]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH3:37])[N:23]=[CH:22][N:21]=2)[CH2:16][C@@H:15]1[OH:38])[C:6](=[O:12])[O:7][C:8]([CH3:10])([CH3:11])[CH3:9])(=[O:3])=[O:4]

参加物

5

反応物 3

HCID 8028TetrahydrofuranHCID 64774Pyridine, hydrofluoride (1:1)2 回HCID 66797969tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}-pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate

生成物 1

HCID 66797857tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-hydroxy-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

反応条件

温度
23 °C

実験手順

To a solution of tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}-pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate (331.5 mg, 0.0004094 mol) in THF (1.84 mL, 0.0228 mol) and pyridine (1.84 mL) at 0° C. was added pyridine hydrofluoride (0.25 mL, 0.0028 mol) dropwise. The mixture was allowed to slowly warm to 23° C. and stirred for 19 hours. To the reaction was added pyridine hydrofluoride (0.25 mL, 0.0028 mol) and the mixture was stirred an additional 6 hours. The reaction was quenched by the dropwise addition of saturated aqueous NaHCO3. The mixture was partitioned with additional saturated aqueous NaHCO3 and EtOAc, separated, and the aqueous was extracted with EtOAc (2×) and CH2Cl2 (2×). The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (30 to 70% EtOAc/hexanes) to collect 34.5 mg (15%) of the title compound. LC/MS: Rt=1.64 min, ES+ 550 (FA standard).

後処理

  1. stirringthe mixture was stirred an additional 6 hours
  2. customThe reaction was quenched by the dropwise addition of saturated aqueous NaHCO3
  3. customThe mixture was partitioned with additional saturated aqueous NaHCO3 and EtOAc
  4. customseparated
  5. extractionthe aqueous was extracted with EtOAc (2×) and CH2Cl2 (2×)
  6. washThe combined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (30 to 70% EtOAc/hexanes)
  11. customto collect 34.5 mg (15%) of the title compound

出典と根拠

ORDレコード
ord-2ca1100f6fff455bae9d04d6dbb266e1
出典データセット
uspto-grants-2013_07
特許番号
US08481550B2

反応ノート

読み込み中…