Nitrogen → Tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate

HRID 1854727Notes

Reaction equation

HRID 1854727 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:11]([C:12]([NH:14][CH3:15])=[O:13])=[C:10]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[O:9][C:5]2=[N:6][C:7]=1[Cl:8].[C:23]([O:27][C:28]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C(=O)([O-])[O-].[Cs+].[Cs+].N#N>O.CN(C=O)C.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>[Cl:8][C:7]1[N:6]=[C:5]2[O:9][C:10]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[C:11]([C:12](=[O:13])[NH:14][CH3:15])[C:4]2=[CH:3][C:2]=1[C:34]1[CH:35]=[C:30]([CH:31]=[CH:32][CH:33]=1)[C:28]([O:27][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:29]

Participants

8

Reactant 4

HCID 947NitrogenHCID 10796Cesium carbonateHCID 2773299(3-((Tert-butoxy)carbonyl)phenyl)boronic acidHCID 904024175-bromo-6-chloro-2-(4-fluorophenyl)-N-methylfuro[2,3-b]pyridine-3-carboxamide

Product 1

HCID 90402329Tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoateYield 88.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 5-bromo-6-chloro-2-(4-fluorophenyl)-N-methylfuro[2,3-b]pyridine-3-carboxamide (5.0 g, 13 mmol), (3-(tert-butoxycarbonyl)phenyl)boronic acid (2.75 g, 12.4 mmol). Pd(Ph3P)4 (2.26 g, 1.96 mmol) and cesium carbonate (8.49 g, 26.1 mmol) was degassed/charged with N2 and diluted with water (22 ml)/DMF (220 ml). The resultant mixture was then degassed, charged with N2, heated to an internal temperature of 65° C. and allowed to stir under N2 atmosphere for 16 h. The reaction mixture was cooled to rt then diluted with EtOAc and sat. 1M HCl. The layers were separated and the aq layer was extracted with EtOAc (3×10 mL). The combined organic extracts were washed with water, brine, dried over Na2SO4 filtered and concentrated. The resultant solid was then flashed on SiO2 eluting with a 0-100% EtOAc in hexanes gradient over 16 CV to give tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate (5.2 g, 11 mmol, 83% yield) as a slightly yellow solid contaminated with the bis-coupled product di-tert-butyl 3,3′-(2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridine-5,6-diyl)dibenzoate. 1H NMR (500 MHz, CHLOROFORM-d) δ 8.18 (s, 1H), 8.08-8.02 (m, 2H), 7.95-7.89 (m, 2H), 7.63 (dt, J=7.6, 1.5 Hz, 1H), 7.52 (t, J=7.6 Hz, 1H), 7.24-7.18 (m, 2H), 6.03 (d, J=4.3 Hz, 1H), 2.99 (d, J=4.9 Hz, 3H), 1.62 (s, 9H).

Workup

  1. customThe resultant mixture was then degassed
  2. additioncharged with N2
  3. temperatureThe reaction mixture was cooled to rt
  4. additionthen diluted with EtOAc and sat. 1M HCl
  5. customThe layers were separated
  6. extractionthe aq layer was extracted with EtOAc (3×10 mL)
  7. washThe combined organic extracts were washed with water, brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b2c3ea186613495bbbc3c36bf362270f
Source dataset
uspto-grants-2015_02
Patent number
US08962651B2

Reaction notes

Loading…