Stannous chloride dihydrate → [(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 2-[5-(hydroxyamino)-1,3-dioxoisoindol-2-yl]acetate

HRID 571285ノート

反応式

HRID 571285 の反応式
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:44])[CH:5]=[C:6]([Cl:43])[C:7]=1[CH2:8][C@@H:9]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH:35]([F:37])[F:36])=[C:30]([O:38][CH2:39][CH:40]2[CH2:42][CH2:41]2)[CH:29]=1)[O:10][C:11](=[O:27])[CH2:12][N:13]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([N+:23]([O-])=[O:24])[CH:19]=2)[C:14]1=[O:26].O.O.[Sn](Cl)Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:44])[CH:5]=[C:6]([Cl:43])[C:7]=1[CH2:8][C@@H:9]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH:35]([F:36])[F:37])=[C:30]([O:38][CH2:39][CH:40]2[CH2:41][CH2:42]2)[CH:29]=1)[O:10][C:11](=[O:27])[CH2:12][N:13]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([NH:23][OH:24])[CH:19]=2)[C:14]1=[O:26]

参加物

4

反応物 2

HCID 61436Stannous chloride dihydrateHCID 86681606HCID 86681606、化合物

生成物 1

HCID 178521246[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 2-[5-(hydroxyamino)-1,3-dioxoisoindol-2-yl]acetate収率 60%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-nitro-1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide (60 mg, 0.092 mmol) was dissolved in THF (5 ml), and added with tin(II) chloride dihydrate (25.0 mg, 0.111 mmol). The reaction was stirred at RT for 18 hours. THF was evaporated under vacuum at RT, and the residue quenched by addition of K2CO3/H2O (15% w/w; 50 ml) and extracted with EtOAc (50 ml). The organic phase was extracted with K2CO3/H2O (15% w/w) (×3), dried over Na2SO4 and the solvent removed under reduced pressure to yield the title compound (35.0 mg, 0.055 mmol, 60% yield). 1H NMR (400 MHz, acetone) ppm 8.80 (bs, 1H), 8.32 (bs, 1H), 8.18 (s, 2H), 7.70 (d, J=8.38 Hz, 1H), 7.36 (d, J=1.76 Hz, 1H), 7.28 (dd, J=8.16, 1.98 Hz, 1H), 7.15-7.23 (m, 2H), 7.03 (dd, J=8.38, 1.76 Hz, 1H), 6.93 (t, 1H, CHF2), 6.13 (dd, J=9.48, 4.63 Hz, 1H), 4.39 (s, 2H), 4.00 (dd, J=7.06, 3.09 Hz, 2H), 3.51 (dd, J=14.33, 9.48 Hz, 1H), 3.31 (dd, J=14.11, 4.41 Hz, 1H), 1.24-1.36 (m, 1H), 0.53-0.71 (m, 2H), 0.31-0.49 (m, 2H). MS/ESI+ [MH]+=637.9

後処理

  1. customTHF was evaporated under vacuum at RT
  2. customthe residue quenched by addition of K2CO3/H2O (15% w/w; 50 ml)
  3. extractionextracted with EtOAc (50 ml)
  4. extractionThe organic phase was extracted with K2CO3/H2O (15% w/w) (×3)
  5. dry with materialdried over Na2SO4
  6. customthe solvent removed under reduced pressure

出典と根拠

ORDレコード
ord-ed717193c262412b95d5992a814f08a7
出典データセット
uspto-grants-2015_05
特許番号
US09024027B2

反応ノート

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