Water → 6-(4-fluoro-3-nitrophenyl)-8-isopropyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 1930312Notes

Reaction equation

HRID 1930312 reaction equation
Br[C:2]1[C:13](=[O:14])[N:12]([CH:15]([CH3:17])[CH3:16])[C:5]2[N:6]=[C:7]([S:10][CH3:11])[N:8]=[CH:9][C:4]=2[CH:3]=1.[F:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][C:20]=1[N+:28]([O-:30])=[O:29].C([O-])([O-])=O.[Na+].[Na+].O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[C:13](=[O:14])[N:12]([CH:15]([CH3:17])[CH3:16])[C:5]3[N:6]=[C:7]([S:10][CH3:11])[N:8]=[CH:9][C:4]=3[CH:3]=2)=[CH:21][C:20]=1[N+:28]([O-:30])=[O:29]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 249017654-Fluoro-3-nitrophenylboronic acidHCID 692975866-bromo-8-isopropyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one

Product 1

HCID 689848066-(4-fluoro-3-nitrophenyl)-8-isopropyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-oneYield 109.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 6-bromo-8-isopropyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)one (0.78 g, 2 mmol; J. Med. Chem., 48, 2371, 2005) in DME (10 ml) was added Pd(PPh3)4 (0.1 g, 5% mol), 4-fluoro-3-nitrophenylboronic acid (0.5 g, 3 mmol) and 2M Na2CO3 solution (3 ml, 6 mmol) and the mixture was heated to 80° C. for 16 h. The mixture was poured into water (40 mL), and product was extracted with EtOAc (3×25 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated in vacuo afforded crude product. Purification by silica gel chromatography provided 6-(4-fluoro-3-nitrophenyl)-8-isopropyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one as off-white solid (0.82 g, 88% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.94 (s, 1H), 8.52 (dd, J=7.2 Hz, 2.4 Hz, 1H), 8.28 (s, 1H), 8.15-8.12 (m, 1H), 7.70 (dd, J=11.6 Hz, 8.8 Hz, 1H), 5.81-5.78 (m, 1H), 2.63 (s, 3H), 1.60 (d, J=6.8 Hz, 6H); MS (ESI) m/z: 375.0 (M+H+).

Workup

  1. extractionwas extracted with EtOAc (3×25 mL)
  2. washThe combined organics were washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customafforded crude product
  6. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-65a181f6d2f3429f904bf620a2f12b88
Source dataset
uspto-grants-2012_05
Patent number
US08188113B2

Reaction notes

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