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1,2-Dichloroethane → N-(3-fluoro-4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 2266361
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HRID 2266361 반응식
[F:1][C:2]1[CH:3]=[C:4]([NH2:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[O:22][N:21]=[C:20]([CH3:23])[N:19]=3)[S:17][C:10]=12.[OH:25][C:26]([CH3:45])([CH3:44])[CH2:27][N:28]1[C:32]([CH3:33])=[C:31]([C:34](O)=[O:35])[C:30](=[O:37])[N:29]1[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl.CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([NH:24][C:34]([C:31]2[C:30](=[O:37])[N:29]([C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[N:28]([CH2:27][C:26]([OH:25])([CH3:45])[CH3:44])[C:32]=2[CH3:33])=[O:35])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]3[O:22][N:21]=[C:20]([CH3:23])[N:19]=3)[S:17][C:10]=12
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참가 물질

8

반응물 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 533934301-(2-Hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydropyrazole-4-carboxylic Acid2회HCID 595983463-Fluoro-4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)thieno[3,2-b]pyridin-7-yloxy)benzenamine2회

생성물 1

HCID 11963145
N-(3-fluoro-4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide
수율 26%

시약·촉매·용매 2

HCID 6212Chloroform용매HCID 6228Dimethylformamide용매

실험 절차

A 16 mm sealed tube was charged with 3-fluoro-4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)thieno[3,2-b]pyridin-7-yloxy)benzenamine (0.0740 g, 0.22 mmol), 1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (0.094 g, 0.32 mmol), EDC (0.062 g, 0.32 mmol), HOBT (0.033 g, 0.22 mmol), Hunig's Base (0.13 ml, 0.76 mmol), and DMF (1.00 ml), sealed, and stirred at room temperature for 18 hours. LC/MS analysis indicated the presence of remaining 3-fluoro-4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)thieno[3,2-b]pyridin-7-yloxy)benzenamine, so additional 1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (0.031 g, 0.11 mmol) was added and the reaction mixture was stirred at 50° C. for 8 hours. The flask was allowed to cool to room temperature, the mixture was diluted with chloroform (25 mL), then washed with water (25 mL), sat. aq. NaHCO3 (25 mL), and brine (25 mL). The organic layer was dried with MgSO4, filtered, and concentrated in vacuo to yield a tan oil. The product was purified by silica gel chromatography eluting with 3% methanol in methylene chloride. The isolated yellow solid was triturated with EtOAc to yield N-(3-fluoro-4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (0.035 g, 26% yield). MS (ESI pos. ion) m/z: 615 (MH+). Calc'd exact mass for C8H4ClNO2S: 614. 1H NMR (400 MHz, DMSO-d6) 11.00 (s, 1H), 8.68 (d, J=5.31 Hz, 1H), 8.49 (s, 1H), 7.96-8.04 (m, 1H), 7.43-7.60 (m, 4H), 7.35 (d, J=8.21 Hz, 3H), 6.89 (d, J=5.31 Hz, 1H), 4.84 (s, 1H), 3.87 (s, 2H), 2.80 (s, 3H), 2.46 (s, 3H), 0.96 (s, 6H).

후처리

  1. customA 16 mm sealed tube
  2. customsealed
  3. additionwas added
  4. stirringthe reaction mixture was stirred at 50° C. for 8 hours
  5. temperatureto cool to room temperature
  6. washwashed with water (25 mL), sat. aq. NaHCO3 (25 mL), and brine (25 mL)
  7. dry with materialThe organic layer was dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto yield a tan oil
  11. customThe product was purified by silica gel chromatography
  12. washeluting with 3% methanol in methylene chloride
  13. customThe isolated yellow solid was triturated with EtOAc

출처 및 근거

ORD 기록
ord-bd6237d5f9b74a4a9a0817b1b22281e4
출처 데이터셋
uspto-grants-2010_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07858623B2

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