Triethylamine → (2R,4R)-2-[2-Fluoro-4-(3-methyl-pyrazol-1-yl)-phenylcarbamoyl]-4-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2217464Notes

Reaction equation

HRID 2217464 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][CH3:14])[CH2:10][C@@H:9]1[C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:18][C:19]1[CH:24]=[C:23]([N:25]2[CH:29]=[CH:28][C:27]([CH3:30])=[N:26]2)[CH:22]=[CH:21][C:20]=1[NH2:31].CCOC1N(C(OCC)=O)C2C(=CC=CC=2)C=C1.CCN(CC)CC>C(Cl)(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][CH3:14])[CH2:10][C@@H:9]1[C:15](=[O:17])[NH:31][C:20]1[CH:21]=[CH:22][C:23]([N:25]2[CH:29]=[CH:28][C:27]([CH3:30])=[N:26]2)=[CH:24][C:19]=1[F:18])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 278332-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinolineHCID 11459222(2R,4R)-1-[(tert-butoxy)carbonyl]-4-methoxypyrrolidine-2-carboxylic acidHCID 221815262-Fluro-4-(3-methyl-pyrazol-1-yl)phenylamine

Product 1

HCID 68805326(2R,4R)-2-[2-Fluoro-4-(3-methyl-pyrazol-1-yl)-phenylcarbamoyl]-4-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

(2R,4R)-4-methoxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (0.350 g, 1.427 mmol), aniline 1 (0.273 g, 1.427 mmol) and EEDQ (0.529 g, 2.140 mmol) were dissolved in CHCl3 (30 mL). Et3N (0.6 mL, 4.281 mmol) was added and the reaction mixture was heated at reflux for 18 h. The mixture was allowed to cool and diluted with CHCl3 (100 mL) and washed with 5% HCl, 0.5 N NaOH, water and brine (40 mL each), the organic extract was dried over MgSO4, filtered and the solvent removed to give a pale tan foam. The crude product was used for the next step without purification. MS: APCI (AP+): 419.2 (M)+, (AP−): 417.2 (M)−.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 18 h
  3. temperatureto cool
  4. washwashed with 5% HCl, 0.5 N NaOH, water and brine (40 mL each)
  5. extractionthe organic extract
  6. dry with materialwas dried over MgSO4
  7. filtrationfiltered
  8. customthe solvent removed
  9. customto give a pale tan foam
  10. customThe crude product was used for the next step without purification

Sources & evidence

ORD record
ord-7b47025a36b146cb81354a41d1e3c5b5
Source dataset
uspto-grants-2008_08
Patent number
US07407972B2

Reaction notes

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