HCID 86752036, compound → HCID 19700382, compound

HRID 861853Notes

Reaction equation

HRID 861853 reaction equation
C([O:8][C:9]([C:11]1[CH:12]=[C:13]([NH:17][C:18](=[O:54])[NH:19][CH2:20][C:21]([N:23]2[CH:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[F:34])[CH:26]([S:35]([C:38]3[CH:43]=[CH:42][C:41]([N+:44]([O-])=O)=[CH:40][CH:39]=3)(=[O:37])=[O:36])[CH2:25][CH:24]2[C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])=[O:22])[CH:14]=[CH:15][CH:16]=1)=[O:10])C1C=CC=CC=1>C(O)C.[Pd]>[NH2:44][C:41]1[CH:40]=[CH:39][C:38]([S:35]([CH:26]2[CH:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[F:34])[N:23]([C:21](=[O:22])[CH2:20][NH:19][C:18](=[O:54])[NH:17][C:13]3[CH:12]=[C:11]([CH:16]=[CH:15][CH:14]=3)[C:9]([OH:10])=[O:8])[CH:24]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH2:25]2)(=[O:37])=[O:36])=[CH:43][CH:42]=1

Participants

4

Reactant 1

HCID 86752036HCID 86752036, compound

Product 1

HCID 19700382HCID 19700382, compoundYield 66.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
20 °C

Procedure

A To a solution of 1.7 g of tert-butyl (2RS,4SR,5RS)-1-{2-[3-(3-benzyloxycarbonylphenyl)ureido]acetyl}-5-(2-fluorophenyl)-4-(4-nitrophenyl)sulphonyl-2-pyrrolidinecarboxylate in 100 cm3 of ethanol is added 0.2 g of 10% palladium-on-charcoal. The suspension is stirred for twenty hours at a temperature in the region of 20° C. under a hydrogen atmosphere (130 kPa). The catalyst is separated out by filtration on Celite and the filtrate is concentrated to dryness under reduced pressure. The residue is purified by chromatography on 40 g of silica contained in a column 2.2 cm in diameter [eluent: dichloromethane/methanol (90/10 by volume)]. The fractions containing the expected product are combined and concentrated under reduced pressure. 0.95 g of (2RS,4SR,5RS)-3-(3-{2-[4-(4-aminophenyl)sulphonyl-2-tert-butoxycarbonyl-5-(2-fluorophenyl)-1-pyrrolidinyl]-2-oxoethyl}ureido)benzoic acid is thus obtained [Rf=0.2; eluent: methylene chloride/methanol (90/10); 1H NMR spectrum (200 MHz, (CD3)2SO with addition of a few drops of CD3COOD, at a temperature of 393 K, δ in ppm): 1.55 (s, 9H: C(CH3)3); from 2.30 to 2.55 and 2.76 (2 mts, 1H each: CH2 at 3); 3.68 and 4.00 (broad d and d respectively, J=17 Hz, 1H each:COCH2N); 3.84 (mt, 1H: H4); 4.62 (t, J=8 Hz, 1H: H2); 5,72 (d, J=3 Hz, 1H: H5); 6.76 (d, J=8 Hz, 2H: H of the aromatic at 4 (H ortho to the NH2)); 7.00 to 7.70 (mt, 6H: aromatic H); 7.58 (d, J=8 Hz, 2H: H of the aromatic at 4 (H meta to the NH2)); 7.82 (broad t, J=8 Hz, 1H: H of the aromatic at 5 (H6)); 8.00 (t, J=1.5 Hz, 1H: aromatic H (H2: ortho to the COOH))].

Workup

  1. customThe catalyst is separated out by filtration on Celite
  2. concentrationthe filtrate is concentrated to dryness under reduced pressure
  3. customThe residue is purified by chromatography on 40 g of silica
  4. additionThe fractions containing the expected product
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3aab4a15a71a4045823c5af0e3e1f79a
Source dataset
uspto-grants-1998_02
Patent number
US05716936

Reaction notes

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