2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide → HCID 87056045, compound

HRID 2201559Notes

Reaction equation

HRID 2201559 reaction equation
Br[C:2]1[CH:20]=[N:19][C:5]2[NH:6][CH2:7][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[C:9](=[O:10])[C:4]=2[CH:3]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[O:29][C:30]3[CH:40]=[C:39]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:44])=[O:43])[C:38](B4OC(C)(C)C(C)(C)O4)=[CH:37][C:31]=3[C:32]=2[C:33]([NH:35][CH3:36])=[O:34])=[CH:24][CH:23]=1>O1CCOCC1.O.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]>[F:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][N:8]2[C:9](=[O:10])[C:4]3[CH:3]=[C:2]([C:38]4[C:39]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:44])=[O:43])=[CH:40][C:30]5[O:29][C:28]([C:25]6[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=6)=[C:32]([C:33]([NH:35][CH3:36])=[O:34])[C:31]=5[CH:37]=4)[CH:20]=[N:19][C:5]=3[NH:6][CH2:7]2)=[CH:13][CH:14]=1

Participants

5

Reactant 2

HCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 117775189HCID 117775189, compound

Product 1

HCID 87056045HCID 87056045, compoundYield 42.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-bromo-3-(4-fluorobenzyl)-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-one (110 mg, 0.33 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (150 mg, 0.30 mmol) and K3PO4.3H2O (159 mg, 0.60 mmol) in dioxane/water (2 mL/0.2 mL) was added Pd(dppf)Cl2 (10 mg) under nitrogen. The mixture was heated at 100° C. for 5 h, and after being concentrated in vacuo, the residue was suspended in water. The suspension was extracted with EtOAc and the organic phase was washed with brine and dried over sodium sulfate. Finally, 5-(3-(4-fluorobenzyl)-4-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (80 mg, yield: 42%) was obtained by the prep-HPLC. 1H-NMR (CDCl3, 400 MHz) δ 8.27˜9.00 (m, 2H), 7.93˜7.96 (m, 2H), 7.80 (s, 1H), 7.64 (s, 1H), 7.33˜7.36 (m, 2H), 7.20 (t, J=8.8 Hz, 2H), 7.05 (t, J=8.4 Hz, 2H), 5.85 (br s, 1H), 5.26 (br s, 1H), 4.72 (s, 4H), 3.19 (s, 3H), 3.02 (d, J=4.8 Hz, 3H), 2.87 (s, 3H). MS (M+H)+: 632.

Workup

  1. concentrationafter being concentrated in vacuo
  2. extractionThe suspension was extracted with EtOAc
  3. washthe organic phase was washed with brine
  4. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-8e763fb8a80246669c9474d022e2eb2c
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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