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Sodium Carbonate → N-{6-[5-{[(2,4-Difluorophenyl)sulfonyl]amino}-6-(methyloxy)-3-pyridinyl]-1-[(4-methylphenyl)sulfonyl]-1H-indazol-4-yl}-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamide

HRID 1695739
ノート
印刷プレビュー

反応式

HRID 1695739 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[C:14]([O:28][CH3:29])=[N:15][CH:16]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:18]=1)(=[O:11])=[O:10].Br[C:31]1[CH:39]=[C:38]2[C:34]([CH:35]=[N:36][N:37]2[S:40]([C:43]2[CH:48]=[CH:47][C:46]([CH3:49])=[CH:45][CH:44]=2)(=[O:42])=[O:41])=[C:33]([NH:50][C:51]([C:53]2[N:54]=[C:55]([CH2:58][N:59]3[CH2:64][C@H:63]([CH3:65])[O:62][C@H:61]([CH3:66])[CH2:60]3)[S:56][CH:57]=2)=[O:52])[CH:32]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:18]=[C:17]([C:31]2[CH:39]=[C:38]3[C:34]([CH:35]=[N:36][N:37]3[S:40]([C:43]3[CH:48]=[CH:47][C:46]([CH3:49])=[CH:45][CH:44]=3)(=[O:42])=[O:41])=[C:33]([NH:50][C:51]([C:53]3[N:54]=[C:55]([CH2:58][N:59]4[CH2:64][C@H:63]([CH3:65])[O:62][C@H:61]([CH3:66])[CH2:60]4)[S:56][CH:57]=3)=[O:52])[CH:32]=2)[CH:16]=[N:15][C:14]=1[O:28][CH3:29])(=[O:10])=[O:11]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 58255797N-{6-Bromo-1-[(4-methylphenyl)sulfonyl]-1H-indazol-4-yl}-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamideHCID 595647052,4-difluoro-N-(2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide

生成物 1

HCID 58255764
N-{6-[5-{[(2,4-Difluorophenyl)sulfonyl]amino}-6-(methyloxy)-3-pyridinyl]-1-[(4-methylphenyl)sulfonyl]-1H-indazol-4-yl}-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamide
収率 51.4%

試薬・触媒・溶媒 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒

反応条件

温度
80 °C

実験手順

2,4-Difluoro-N-[2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]benzenesulfonamide (116 mg), N-{6-bromo-1-[(4-methylphenyl)sulfonyl]-1H-indazol-4-yl}-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamide (150 mg), Pd(dppf)Cl2 (18 mg), sodium carbonate (79 mg), 1,4-dioxane (5 ml) and water (5 ml) were combined and heated at 80° C. for 3 hours. The cooled reaction mixture was filtered through a 1 g silica cartridge, washing with methanol, then evaporated to dryness. The residue was dissolved in DCM and washed with water. The DCM was passed through a hydrophobic frit and evaporated to dryness. The residue was purified by ISCO companion, 12 g Silica cartridge using 0-5% MeOH in DCM over 16 mins. Pure fractions were combined and evaporated to give title compound, (105 mg).

後処理

  1. customThe cooled reaction mixture
  2. filtrationwas filtered through a 1 g silica cartridge
  3. washwashing with methanol
  4. customevaporated to dryness
  5. dissolutionThe residue was dissolved in DCM
  6. washwashed with water
  7. customevaporated to dryness
  8. customThe residue was purified by ISCO companion, 12 g Silica cartridge
  9. customover 16 mins
  10. customevaporated

出典と根拠

ORDレコード
ord-2ec28384a3ae4b8d8a37c3617cbda0eb
出典データセット
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08163743B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート