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 1776900Notes

Reaction equation

HRID 1776900 reaction equation
[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

Participants

7

Reactant 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

Product 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-carboxamideYield 53%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-2030470ac69844988021883c8fdec586
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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