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Sodium Carbonate → 3-{[Bis(benzyloxy)phosphoryl]oxy}propyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate

HRID 1047122
ノート
印刷プレビュー

反応式

HRID 1047122 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([CH2:12][CH3:13])[CH:7]=[C:6]([C:14]([O:16][CH2:17][CH2:18][CH2:19][O:20][P:21]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22])=[O:15])[C:5]2=[O:39].[CH2:40]([NH:42][C:43](=[O:63])[NH:44][C:45]1[N:50]=[CH:49][C:48](B(O)O)=[C:47]([C:54]2[S:55][CH:56]=[C:57]([C:59]([F:62])([F:61])[F:60])[N:58]=2)[CH:46]=1)[CH3:41].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:12]([N:8]1[C:9]2[C:4](=[CH:3][C:2]([C:48]3[CH:49]=[N:50][C:45]([NH:44][C:43](=[O:63])[NH:42][CH2:40][CH3:41])=[CH:46][C:47]=3[C:54]3[S:55][CH:56]=[C:57]([C:59]([F:62])([F:60])[F:61])[N:58]=3)=[CH:11][N:10]=2)[C:5](=[O:39])[C:6]([C:14]([O:16][CH2:17][CH2:18][CH2:19][O:20][P:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([O:31][CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[O:22])=[O:15])=[CH:7]1)[CH3:13]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 594161896-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid2 回HCID 687490433-{[Bis(benzyloxy)phosphoryl]oxy}propyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate2 回

生成物 1

HCID 687463213-{[Bis(benzyloxy)phosphoryl]oxy}propyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate
収率 65%

試薬・触媒・溶媒 2

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 6228Dimethylformamide溶媒

実験手順

3-{[Bis(benzyloxy)phosphoryl]oxy}propyl 6-bromo-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (Intermediate 26, 750 mg, 1.21 mmol) was dissolved in dimethylformamide (25 mL) and the solution was purged with argon. Tetrakis (triphenylphosphine) palladium (145 mg, 0.12 mmol) followed by 6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 9, 645 mg, 1.46 mmol) was added and the mixture was stirred for 20 min at room temperature. Sodium carbonate solution (516 mg, 4.87 mmol) (dissolved in minimum amount of water) was added to reaction mixture and it was heated to 90° C. for 3 h. The reaction mixture was passed through celite bed and the celite was washed with dimethylformamide. The dimethylformamide layer was poured into water (100 mL) and a precipitate formed. The solid was filtered and dried then purified by flash column chromatography over silica gel (100-200 mesh). The product was eluted with gradient of MeOH/CHCl3 (0-6%) to afford 650 mg (65%) 3-{[bis(benzyloxy)phosphoryl]oxy}propyl 1-ethyl-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate as white solid.

後処理

  1. customthe solution was purged with argon
  2. additionwas added
  3. temperaturewas heated to 90° C. for 3 h
  4. washthe celite was washed with dimethylformamide
  5. additionThe dimethylformamide layer was poured into water (100 mL)
  6. customa precipitate formed
  7. filtrationThe solid was filtered
  8. customdried
  9. customthen purified by flash column chromatography over silica gel (100-200 mesh)
  10. washThe product was eluted with gradient of MeOH/CHCl3 (0-6%)

出典と根拠

ORDレコード
ord-2dd94b3cbee9494ea0080ff054a3763f
出典データセット
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08569484B2

反応ノート

読み込み中…

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