Dichloromethane → methyl 5-(4-{[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenyl]thio}pyridin-2-yl)-1H-pyrrole-3-carboxylate

HRID 521797Notes

Reaction equation

HRID 521797 reaction equation
Cl[C:2]1[CH:7]=[C:6]([S:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][C:20]=3[F:26])=[O:17])=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:35]2[NH:39][CH:38]=[C:37]([C:40]([O-:42])=[O:41])[CH:36]=2)O1.[CH2:44](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]>[F:26][C:20]1[CH:21]=[CH:22][C:23]([CH3:25])=[CH:24][C:19]=1[NH:18][C:16]([NH:15][C:12]1[CH:13]=[CH:14][C:9]([S:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:35]3[NH:39][CH:38]=[C:37]([C:40]([O:42][CH3:44])=[O:41])[CH:36]=3)[CH:7]=2)=[CH:10][CH:11]=1)=[O:17]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 581677791-[4-(2-Chloro-pyridin-4-ylsulfanyl)-phenyl]-3-(2-fluoro-5-methyl-phenyl)-ureaHCID 866515565-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-3-carboxylate

Product 1

HCID 67042749methyl 5-(4-{[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenyl]thio}pyridin-2-yl)-1H-pyrrole-3-carboxylateYield 20%

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 1-[4-(2-Chloro-pyridin-4-ylsulfanyl)-phenyl]-3-(2-fluoro-5-methyl-phenyl)-urea (410 mg, 1.06 mmol), methyl-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-3-carboxylate (532 mg, 2.12 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 (1.0 mL) was added, followed by DMSO (10 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 silica gel chromatography eluting with 2-5% MeOH/CHCl3 to afford methyl 5-(4-{[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenyl]thio}pyridin-2-yl)-1H-pyrrole-3-carboxylate as off-white solid. Yield: 100 mg, 20% yield.

Workup

  1. custompurged with N2
  2. additionA solution of 2M Na2CO3 (1.0 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 silica gel chromatography
  11. washeluting with 2-5% MeOH/CHCl3

Sources & evidence

ORD record
ord-44169bb3b0054687af66cfd99d8ca027
Source dataset
uspto-grants-2016_05
Patent number
US09328103B2

Reaction notes

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