(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonate → (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ((S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-yl)carbamate

HRID 339084ノート

反応式

HRID 339084 の反応式
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C@H:7]([C:12]2[CH:13]=[CH:14][C:15]3[N:16]([C:18]([C:21]4[CH:30]=[CH:29][C:28]5[C:23](=[CH:24][C:25]([O:32][CH2:33][CH2:34][OH:35])=[C:26]([F:31])[CH:27]=5)[N:22]=4)=[N:19][N:20]=3)[CH:17]=2)[C:8]([F:11])([F:10])[F:9])[CH2:3]1.[C:36](=O)([O:46]C1C=CC([N+]([O-])=O)=CC=1)[O:37][CH2:38][C:39]1[O:40][C:41](=[O:45])[O:42][C:43]=1[CH3:44]>CN(C=O)C>[F:10][C:8]([F:9])([F:11])[C@H:7]([N:4]1[CH2:5][CH2:6][C@H:2]([NH:1][C:36](=[O:46])[O:37][CH2:38][C:39]2[O:40][C:41](=[O:45])[O:42][C:43]=2[CH3:44])[CH2:3]1)[C:12]1[CH:13]=[CH:14][C:15]2[N:16]([C:18]([C:21]3[CH:30]=[CH:29][C:28]4[C:23](=[CH:24][C:25]([O:32][CH2:33][CH2:34][OH:35])=[C:26]([F:31])[CH:27]=4)[N:22]=3)=[N:19][N:20]=2)[CH:17]=1

参加物

4

反応物 2

HCID 10756264(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonateHCID 709845612-(2-(6-((R)-1-((S)-3-aminopyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoro quinolin-7-yloxy)ethanol

生成物 1

HCID 70984291(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ((S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-yl)carbamate収率 80%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a solution of 2-((2-(6-((R)-1-((S)-3-aminopyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoro quinolin-7-yl)oxy)ethanol (125 mg, 0.255 mmol) in DMF (1.5 mL) was added a solution of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonate (prepared according to procedures described in J. Med. Chem. 1999, 42, 3994-4000, 71.2 mg, 0.255 mmol) in DMF (1 mL). The reaction mixture was stirred at ambient temperature for 30 minutes. The reaction was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with water and brine, dried and concentrated. The residue was purified by flash chromatography on silica gel (DCM:MeOH, 70:1 to 40:1) to give (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ((S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-yl)carbamate (131 mg, 80%). LCMS APCI (+) m/z 647 (M+H).

後処理

  1. customThe reaction was partitioned between EtOAc and water
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washThe combined organic layers were washed with water and brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel (DCM:MeOH, 70:1 to 40:1)

出典と根拠

ORDレコード
ord-22de57705a584fbd841505fed5a0520b
出典データセット
uspto-grants-2014_11
特許番号
US08889704B2

反応ノート

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