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Diisopropylcarbodiimide → 1-(4-(2-(4-Chlorophenyl)-7-oxothieno[2,3-d]pyridazin-6(7H)-yl)-2-methoxyphenoxy)-2-methylpropan-2-yl 2-(tert-butoxycarbonylamino)acetate

HRID 2263662
ノート
印刷プレビュー

反応式

HRID 2263662 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:31][C:11]3[C:12](=[O:30])[N:13]([C:16]4[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]([OH:27])([CH3:26])[CH3:25])=[C:18]([O:28][CH3:29])[CH:17]=4)[N:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.[C:32]([NH:39][CH2:40][C:41](O)=[O:42])([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].C(N=C=NC(C)C)(C)C>C(Cl)Cl>[C:35]([O:34][C:32]([NH:39][CH2:40][C:41]([O:27][C:24]([CH3:26])([CH3:25])[CH2:23][O:22][C:19]1[CH:20]=[CH:21][C:16]([N:13]2[C:12](=[O:30])[C:11]3[S:31][C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)=[CH:9][C:10]=3[CH:15]=[N:14]2)=[CH:17][C:18]=1[O:28][CH3:29])=[O:42])=[O:33])([CH3:38])([CH3:37])[CH3:36]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 12734DiisopropylcarbodiimideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 251172722-(4-chlorophenyl)-6-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)thieno[2,3-d]pyridazin-7(6H)-one

生成物 1

HCID 251172741-(4-(2-(4-Chlorophenyl)-7-oxothieno[2,3-d]pyridazin-6(7H)-yl)-2-methoxyphenoxy)-2-methylpropan-2-yl 2-(tert-butoxycarbonylamino)acetate

試薬・触媒・溶媒 1

HCID 6344
Dichloromethane
溶媒

実験手順

To a solution of 2-(4-chlorophenyl)-6-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)thieno[2,3-d]pyridazin-7(6H)-one (100 mg, 0.219 mmol) that was prepared in Example 9,4-(pyrrolidin-1-yl)pyridine (32.4 mg, 0.219 mmol) and boc-glycine (192 mg, 1.094 mmol) in CH2Cl2 (10 ml) was added N,N′-diisopropylcarbodiimide (0.170 ml, 1.094 mmol). The mixture was stirred at reflux for 1 hours and then at RT for 18 hours. LC-MS analysis revealed desired product as well as the imide resulting from condensation with a second Boc-glycine. The later product was cleaved to regenerate desired product by addition of hydrazine (0.343 ml, 10.94 mmol) was added and the stirring at RT for 30 min. The reaction was diluted with a solution of saturated NaHCO3 (15 ml) and extracted with CH2Cl2 (20 ml). The CH2Cl2 extracts were dried over Na2SO4 and concentrated. The crude product was purified by ISCO chromatography on two silica gel column (2×12 g) employing a 10 min gradient ranging from hexane to 100% ethyl acetate to elute 1-(4-(2-(4-chlorophenyl)-7-oxothieno[2,3-d]pyridazin-6(7H)-yl)-2-methoxyphenoxy)-2-methylpropan-2-yl 2-(tert-butoxycarbonylamino)acetate (130 mg, 0.212 mmol, 97% yield) as light brown solid.

後処理

  1. temperatureat reflux for 1 hours

出典と根拠

ORDレコード
ord-9871827d281241efbe5dc4fc67c8a995
出典データセット
uspto-grants-2010_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07851622B2

反応ノート

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