Pyrrolidine → 2-(5-{3-[2-Fluoro-4-(pyrrolidin-1-ylcarbonyl)phenoxy]-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-1H-pyrrol-2-yl)-1,3-thiazole

HRID 909508Notes

Reaction equation

HRID 909508 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][C:12]1[CH:17]=[C:16]([C:18]2[NH:19][C:20]([C:23]3[S:24][CH:25]=[CH:26][N:27]=3)=[CH:21][CH:22]=2)[CH:15]=[C:14]([O:28][C@@H:29]([CH3:33])[CH2:30][O:31][CH3:32])[CH:13]=1)[C:5](O)=[O:6].[NH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>O1CCCC1.[Cl-].[Na+].O>[F:1][C:2]1[CH:3]=[C:4]([C:5]([N:34]2[CH2:38][CH2:37][CH2:36][CH2:35]2)=[O:6])[CH:8]=[CH:9][C:10]=1[O:11][C:12]1[CH:17]=[C:16]([C:18]2[NH:19][C:20]([C:23]3[S:24][CH:25]=[CH:26][N:27]=3)=[CH:21][CH:22]=2)[CH:15]=[C:14]([O:28][C@@H:29]([CH3:33])[CH2:30][O:31][CH3:32])[CH:13]=1

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666824973-Fluoro-4-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}benzoic acid

Product 1

HCID 580654552-(5-{3-[2-Fluoro-4-(pyrrolidin-1-ylcarbonyl)phenoxy]-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-1H-pyrrol-2-yl)-1,3-thiazoleYield 72.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

3-Fluoro-4-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}benzoic acid (40.0 mg, 0.085 mmol) synthesized in Example (44a) was dissolved in tetrahydrofuran (5 mL), and pyrrolidine (21 μL, 0.26 mmol), HATU (64.9 mg, 0.171 mmol) and N,N-diisopropylethylamine (89 μL, 0.51 mmol) were added, followed by stirring at room temperature for 20 hours under nitrogen atmosphere. To the reaction solution, saturated brine (15 mL) was added, and extraction was carried out twice with ethyl acetate (15 mL), followed by drying over sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-75%) to afford the desired compound (32 mg, yield 72%) as a white solid.

Workup

  1. extractionextraction
  2. dry with materialby drying over sodium sulfate
  3. distillationThe solvent was distilled off under reduced pressure
  4. customthe resulting residue was purified
  5. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=0%-75%)

Sources & evidence

ORD record
ord-200f425d4404498d9cc26028d84bc688
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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