Cesium carbonate → 7-[(R)-1-(2,6-dichloro-3-fluorophenyl)-ethoxy]-3-phenyl-furo[3,2-c]pyridin-6-ylamine

HRID 911953Notes

Reaction equation

HRID 911953 reaction equation
Br[C:2]1[C:6]2[CH:7]=[N:8][C:9]([NH2:23])=[C:10]([O:11][C@@H:12]([C:14]3[C:19]([Cl:20])=[CH:18][CH:17]=[C:16]([F:21])[C:15]=3[Cl:22])[CH3:13])[C:5]=2[O:4][CH:3]=1.[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.CCOC(C)=O.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:22][C:15]1[C:16]([F:21])=[CH:17][CH:18]=[C:19]([Cl:20])[C:14]=1[C@H:12]([O:11][C:10]1[C:5]2[O:4][CH:3]=[C:2]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:6]=2[CH:7]=[N:8][C:9]=1[NH2:23])[CH3:13]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 578127253-Bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine

Product 1

HCID 578127697-[(R)-1-(2,6-dichloro-3-fluorophenyl)-ethoxy]-3-phenyl-furo[3,2-c]pyridin-6-ylamineYield 41.5%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)-ethoxy]-furo[3,2-c]pyridin-6-ylamine (25 mg, 0.0595 mmol), phenylboronic acid (8.7 mg, 0.071 mmol), Cs2CO3 (58 mg, 0.18 mmol), and Pd(PPh3)4 (6.9 mg, 0.006 mmol) in DME (1.5 mL) and H2O (0.5 mL) was degassed and refilled with nitrogen (3×). This mixture was then heated at 100° C. using microwave for 30 min. LC-MS showed completion of the reaction. The reaction mixture was diluted with EtOAc (30 mL), washed with brine (10 mL), and dried over anhydrous sodium sulfate. The residue was purified by silica gel chromatography (Hexane:EtOAc=70:30) to give a brown oil, which was further purified by mass-directed purification to afford the title compound as a brown oil (10.3 mg). 1H NMR (CDCl3, 400 MHz): δ=1.93 (d, J=6.8 Hz, 3H), 6.70 (q, J=6.8 Hz, 1H), 7.10 (dd, J=9.1, 7.8 Hz, 1H), 7.33 (dd, J=9.1, 4.8 Hz, 1H), 7.42-7.55 (m, 5H), 7.67 (s, 1H), 8.12 (s, 1H), 8.18 (s, 1H). MS (ES+): 417.01/418.99 [MH+].

Workup

  1. customwas degassed
  2. additionrefilled with nitrogen (3×)
  3. customfor 30 min
  4. customcompletion of the reaction
  5. washwashed with brine (10 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe residue was purified by silica gel chromatography (Hexane:EtOAc=70:30)
  8. customto give a brown oil, which
  9. customwas further purified by mass-directed purification

Sources & evidence

ORD record
ord-85ac879c5ab44d9284beda6d15e8a873
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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