Sodium Hydroxide → (+/-)-3-[2-(4-Hydroxy-piperidin-1-yl)-thiazol-4-yl]-3-[4-(7-methoxy-quinolin-8-yl)-[1,4]diazepan-1-yl]-propionic acid methyl ester

HRID 532838ノート

反応式

HRID 532838 の反応式
[N:1]1([C:8]2[C:9]([O:18][CH3:19])=[CH:10][CH:11]=[C:12]3[C:17]=2[N:16]=[CH:15][CH:14]=[CH:13]3)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[OH:20][CH:21]1[CH2:26][CH2:25][N:24]([C:27]2[S:28][CH:29]=[C:30]([CH:32]=O)[N:31]=2)[CH2:23][CH2:22]1.C([Si]([O:41][C:42]([O:44][CH3:45])=[CH2:43])(C)C)(C)(C)C.C([O-])(O)=O.[Na+].[OH-].[Na+]>C(Cl)Cl.ClCCCl>[CH3:45][O:44][C:42](=[O:41])[CH2:43][CH:32]([C:30]1[N:31]=[C:27]([N:24]2[CH2:23][CH2:22][CH:21]([OH:20])[CH2:26][CH2:25]2)[S:28][CH:29]=1)[N:4]1[CH2:5][CH2:6][CH2:7][N:1]([C:8]2[C:9]([O:18][CH3:19])=[CH:10][CH:11]=[C:12]3[C:17]=2[N:16]=[CH:15][CH:14]=[CH:13]3)[CH2:2][CH2:3]1

参加物

8

反応物 5

HCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 45644911-(tert-Butyldimethylsilyloxy)-1-methoxyetheneHCID 593661612-(4-Hydroxy-piperidin-1-yl)-thiazole-4-carbaldehydeHCID 593661628-(1,4-Diazepan-1-yl)-7-methoxyquinoline

生成物 1

HCID 59366202(+/-)-3-[2-(4-Hydroxy-piperidin-1-yl)-thiazol-4-yl]-3-[4-(7-methoxy-quinolin-8-yl)-[1,4]diazepan-1-yl]-propionic acid methyl ester収率 38%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
55 °C

実験手順

1,2-Dichloroethane (1.02 mL) was added to a mixture of 8-[1,4]diazepan-1-yl-7-methoxy-quinoline (1.00 g, 3.88 mmol) and 2-(4-hydroxy-piperidin-1-yl)-thiazole-4-carbaldehyde (824 mg, 3.88 mmol). The reaction was heated to 55° C. and stirred until homogeneous. Freshly crushed Ti(OMe)4 (1.00 g, 5.82 mmol) was then added and the reaction was stirred at 55° C. for 1 h. tert-Butyl-(1-methoxy-vinyloxy)-dimethyl-silane (1.02 mL, 4.66 mmol) was then added and the reaction was stirred at 55° C. for 18 h. CH2Cl2 was then added, followed by sat. aq. NaHCO3, then 1 N aq. NaOH. This mixture was then stirred for 5 min and filtered through celite, washing the filter cake with CH2Cl2. The filtrate was then washed once with H2O, dried over MgSO4, filtered, and concentrated. The crude product was purified on silica gel (99:1 to 90:10 CH2Cl2:(9:1 MeOH:NH4OH)) to give the product (660 mg, 38% yield).

後処理

  1. additionwas then added
  2. stirringthe reaction was stirred at 55° C. for 18 h
  3. stirringThis mixture was then stirred for 5 min
  4. filtrationfiltered through celite
  5. washwashing the filter cake with CH2Cl2
  6. washThe filtrate was then washed once with H2O
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified on silica gel (99:1 to 90:10 CH2Cl2:(9:1 MeOH:NH4OH))

出典と根拠

ORDレコード
ord-2254de526a4342c0baf15f2cc23136b7
出典データセット
uspto-grants-2014_10
特許番号
US08853202B2

反応ノート

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