Dichloromethane → 5-{4-[3-(2-Fluoro-5-methyl-phenylcarbamoyl)-phenoxy]-pyridin-2-yl}-1H-pyrrole-3-carboxylic acid methyl ester

HRID 521776Notes

Reaction equation

HRID 521776 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]([CH:23]=[CH:24][CH:25]=2)[C:12]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][C:16]=2[F:22])=[O:13])[CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:34]2[NH:38][CH:37]=[C:36]([C:39]([O-:41])=[O:40])[CH:35]=2)O1.[CH2:43](Cl)Cl>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]>[CH3:43][O:41][C:39]([C:36]1[CH:35]=[C:34]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:25]=[CH:24][CH:23]=[C:11]([C:12](=[O:13])[NH:14][C:15]4[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][C:16]=4[F:22])[CH:10]=3)[CH:5]=[CH:4][N:3]=2)[NH:38][CH:37]=1)=[O:40]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 581678683-(2-bromo-pyridin-4-yloxy)-N-(2-fluoro-5-methyl-phenyl)-benzamideHCID 866515565-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-3-carboxylate

Product 1

HCID 510016275-{4-[3-(2-Fluoro-5-methyl-phenylcarbamoyl)-phenoxy]-pyridin-2-yl}-1H-pyrrole-3-carboxylic acid methyl esterYield 2,806.2%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
95 °C

Procedure

A mixture of 3-(2-bromo-pyridin-4-yloxy)-N-(2-fluoro-5-methyl-phenyl)-benzamide (200 mg, 0.50 mmol), methyl-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-3-carboxylate (251 mg, 1.0 mmol) and PdCl2(dppf).CH2Cl2 (10 mg, 0.012 mmol) was added to a thick-walled reaction vessel and purged with N2. A solution of 2M Na2CO3 (0.5 mL) was added, followed by DMSO (8 mL). The reaction vessel was sealed and the mixture stirred at 95° C. for 16 h. The reaction vessel was cooled to room temperature and the mixture was poured into 100 ml of water. The precipitates were filtered, washed with water and dried to give the crude, which was purified via column chromatography eluting with 30-40% EtOAc/hexanes to afford 5-{4-[3-(2-Fluoro-5-methyl-phenylcarbamoyl)-phenoxy]-pyridin-2-yl}-1H-pyrrole-3-carboxylic acid methyl ester (150 mg, 58% yield).

Workup

  1. custompurged with N2
  2. additionA solution of 2M Na2CO3 (0.5 mL) was added
  3. customThe reaction vessel was sealed
  4. temperatureThe reaction vessel was cooled to room temperature
  5. additionthe mixture was poured into 100 ml of water
  6. filtrationThe precipitates were filtered
  7. washwashed with water
  8. customdried
  9. customto give the crude, which
  10. customwas purified via column chromatography
  11. washeluting with 30-40% EtOAc/hexanes

Sources & evidence

ORD record
ord-dcb608e4832641a497643cd16d278e14
Source dataset
uspto-grants-2016_05
Patent number
US09328103B2

Reaction notes

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