Potassium Phosphate, Tribasic → 5-(5-(benzyloxy)-6-(3-(hydroxymethyl)pyrazolo[1,5-a]pyridin-2-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 1776900노트

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HRID 1776900 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18](C4C=CC=C(B5OC(C)(C)C(C)(C)O5)C=4)=[CH:17][C:11]=3[C:12]=2[C:13]([NH:15][CH3:16])=[O:14])=[CH:4][CH:3]=1.[CH2:42]([O:49][C:50]1[C:51]([C:57]2[C:65]([CH2:66][OH:67])=[C:60]3[CH:61]=[CH:62][CH:63]=[CH:64][N:59]3[N:58]=2)=[N:52][C:53](Cl)=[CH:54][CH:55]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:42]([O:49][C:50]1[CH:55]=[CH:54][C:53]([C:18]2[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:23])=[O:24])=[CH:20][C:10]3[O:9][C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[C:12]([C:13]([NH:15][CH3:16])=[O:14])[C:11]=3[CH:17]=2)=[N:52][C:51]=1[C:57]1[C:65]([CH2:66][OH:67])=[C:60]2[CH:61]=[CH:62][CH:63]=[CH:64][N:59]2[N:58]=1)[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

참가 물질

7

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 674032762-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzofuran-3-carboxamideHCID 86728284(2-(3-(Benzyloxy)-6-chloropyridin-2-yl)pyrazolo[1,5-a]pyridin-3-yl)methanol

생성물 1

HCID 712954825-(5-(benzyloxy)-6-(3-(hydroxymethyl)pyrazolo[1,5-a]pyridin-2-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide수율 53%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 218864351,4-Dioxane--water (1/1)용매

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온도
100 °C

실험 절차

To a degassed solution of 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzofuran-3-carboxamide (452 mg, 0.90 mmol) and compound (2-(3-(benzyloxy)-6-chloropyridin-2-yl)pyrazolo[1,5-a]pyridin-3-yl)methanol (300 mg, 0.82 mmol) in dioxane/H2O (5 mL/1 mL) was added Pd2(dba)3 (90 mg, 0.1 mmol), X-Phos (95 mg, 0.2 mmol) and K3PO4 (1.2 g, 2.4 mmol) under N2. After stirred at 100° C. overnight, the reaction mixture was cooled to room temperature and filtered. The filtrate was washed with brine and dried over Na2SO4. After concentrated, the resulting residue was purified using column chromatography (petroleum ether:ethyl acetate=1:2) to provide the product of compound 5-(5-(benzyloxy)-6-(3-(hydroxymethyl)pyrazolo[1,5-a]pyridin-2-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (300 mg, yield: 53%). 1H-NMR (Methanol-d4, 400 MHz) δ 8.47 (d, J=8.8 Hz, 1H), 8.00 (dd, J=5.2, 8.8 Hz, 2H), 7.76 (d, J=8.8 Hz, 1H), 7.68 (d, J=9.2 Hz, 1H), 7.63 (d, J=8.4 Hz, 1H), 7.30˜7.24 (m, 7H), 7.16˜7.11 (m, 1H), 7.13 (dt, J=0.8, 6.8 Hz, 1H), 5.22 (s, 2H), 4.74 (s, 2H), 3.29 (s, 3H), 2.93 (s, 3H), 2.89 (s, 3H). MS (M+H)+: 706.

후처리

  1. temperaturethe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationAfter concentrated
  6. customthe resulting residue was purified

출처 및 근거

ORD 기록
ord-2030470ac69844988021883c8fdec586
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09265773B2

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