Trifluoroacetic acid → 3-methyl-N-(4-{[2-(1H-pyrrol-2-yl)pyridin-4-yl]oxy}phenyl)-2-furamide

HRID 1915062Notes

Reaction equation

HRID 1915062 reaction equation
[CH3:1][C:2]1[CH:6]=[CH:5][O:4][C:3]=1[C:7]([OH:9])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:34][C:35]1[CH:59]=[CH:58][C:38]([O:39][C:40]2[CH:45]=[CH:44][N:43]=[C:42]([C:46]3[N:47](C(OC(C)(C)C)=O)[CH:48]=[CH:49][CH:50]=3)[CH:41]=2)=[CH:37][CH:36]=1.C(N(CC)C(C)C)(C)C.FC(F)(F)C(O)=O>CN(C=O)C.C(Cl)Cl.O>[CH3:1][C:2]1[CH:6]=[CH:5][O:4][C:3]=1[C:7]([NH:34][C:35]1[CH:36]=[CH:37][C:38]([O:39][C:40]2[CH:45]=[CH:44][N:43]=[C:42]([C:46]3[NH:47][CH:48]=[CH:49][CH:50]=3)[CH:41]=2)=[CH:58][CH:59]=1)=[O:9]

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 781273-Methyl-2-furoic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58167895tert-butyl 2-[4-(4-aminophenoxy)pyridin-2-yl]-1H-pyrrole-1-carboxylate

Product 1

HCID 670425593-methyl-N-(4-{[2-(1H-pyrrol-2-yl)pyridin-4-yl]oxy}phenyl)-2-furamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-methyl-2-furoic acid (70 mg, 0.55 mmol), HATU (243 mg, 0.64 mmol),) tert-butyl 2-[4-(4-aminophenoxy)pyridin-2-yl]-1H-pyrrole-1-carboxylate (160 mg, 0.46 mmol) and N,N-diisopropylethylamine (148 mg, 1.15 mmol) in anhydrous DMF (10 ml) was stirred at 45° C. for 2 hours. The mixture was poured into 100 ml of water. The precipitates were filtered, washed with water and dried in vacuo to give the crude, which was dissolved in 5 ml of methylene chloride, followed by addition of trifluoroacetic acid (3 ml). The mixture was stirred at room temperature for 16 hours. The solvents were evaporated under reduced pressure. The residue was purified by reversed-phase chromatography with a gradient of 10˜50% acetonitrile/water to give 3-methyl-N-(4-{[2-(1H-pyrrol-2-yl)pyridin-4-yl]oxy}phenyl)-2-furamide as white solid. Yield: 56 mg, 34%.

Workup

  1. filtrationThe precipitates were filtered
  2. washwashed with water
  3. customdried in vacuo
  4. customto give the crude, which
  5. customThe solvents were evaporated under reduced pressure
  6. customThe residue was purified by reversed-phase chromatography with a gradient of 10˜50% acetonitrile/water

Sources & evidence

ORD record
ord-6f83c1ad0ea847878b99a0c283ef9dcf
Source dataset
uspto-grants-2013_12
Patent number
US08614234B2

Reaction notes

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