Diisopropylethylamine → 1-{1-[(2'-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3-fluorobiphenyl-4-yl)carbonyl]piperidin-4-yl}-7-chloro-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one

HRID 1026565ノート

反応式

HRID 1026565 の反応式
[Si:1]([O:18][CH2:19][CH2:20][C@H:21]([O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]1[CH:35]=[CH:34][C:33]([C:36](O)=[O:37])=[C:32]([F:39])[CH:31]=1)[CH3:22])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[Cl:47][C:48]1[CH:57]=[C:56]2[C:51]([CH2:52][C:53]([CH3:66])([CH3:65])[C:54](=[O:64])[N:55]2[CH:58]2[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]2)=[N:50][CH:49]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>C(OCC)(=O)C.CN(C)C=O>[Si:1]([O:18][CH2:19][CH2:20][C@H:21]([O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]1[CH:35]=[CH:34][C:33]([C:36]([N:61]2[CH2:60][CH2:59][CH:58]([N:55]3[C:56]4[C:51](=[N:50][CH:49]=[C:48]([Cl:47])[CH:57]=4)[CH2:52][C:53]([CH3:65])([CH3:66])[C:54]3=[O:64])[CH2:63][CH2:62]2)=[O:37])=[C:32]([F:39])[CH:31]=1)[CH3:22])([C:14]([CH3:15])([CH3:16])[CH3:17])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 680061317-chloro-3,3-dimethyl-1-piperidin-4-yl-3,4-dihydro-1,5-naphthyridin-2(1H)-one trifluoroacetateHCID 680062692'-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3-fluorobiphenyl-4-carboxylic acid

生成物 1

HCID 680062751-{1-[(2'-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3-fluorobiphenyl-4-yl)carbonyl]piperidin-4-yl}-7-chloro-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one収率 90.8%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To an N,N-dimethylformamide solution (6 ml) of 2′-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3-fluorobiphenyl-4-carboxylic acid (387 mg) were added at room temperature 7-chloro-3,3-dimethyl-1-piperidin-4-yl-3,4-dihydro-1,5-naphthyridin-2(1H)-one trifluoroacetate (Reference Example 10) (291 mg), diisopropylethylamine (0.497 ml) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (298 mg), followed by stirring overnight. The reaction solution was diluted with ethyl acetate, washed sequentially with a 10% aqueous citric acid solution, a saturated aqueous sodium hydrogen carbonate solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford 1-{1-[(2′-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3-fluorobiphenyl-4-yl)carbonyl]piperidin-4-yl}-7-chloro-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one (530 mg).

後処理

  1. washwashed sequentially with a 10% aqueous citric acid solution
  2. dry with materiala saturated aqueous sodium hydrogen carbonate solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-8089c916a4124a78b2bf3e002b7148c4
出典データセット
uspto-grants-2014_05
特許番号
US08729095B2

反応ノート

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