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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
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인쇄 미리보기

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HRID 1695739 반응식
[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]
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참가 물질

7

반응물 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

생성물 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
수율 51.4%

시약·촉매·용매 2

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

반응 조건

온도
80 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-2ec28384a3ae4b8d8a37c3617cbda0eb
출처 데이터셋
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08163743B2

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