Tetrahydrofuran → HCID 15384043, compound

HRID 2293796Notes

Reaction equation

HRID 2293796 reaction equation
[NH2:1][CH2:2][C:3]([N:5]1[C@@H:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:16])[C@H:8]([C:17]([O:19][CH3:20])=[O:18])[S:7][C@H:6]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:4].O1[CH2:32][CH2:31][CH2:30][CH2:29]1>CC1C=C(N=C=O)C=CC=1>[CH3:20][O:19][C:17]([C@@H:8]1[S:7][C@@H:6]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[N:5]([C:3](=[O:4])[CH2:2][NH:1][C:3]([NH:5][C:9]2[CH:10]=[CH:32][CH:31]=[C:30]([CH3:29])[CH:8]=2)=[O:4])[C@H:9]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[F:16])=[O:18]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 86751601HCID 86751601, compound

Product 1

HCID 15384043HCID 15384043, compound

Reagents, catalysts & solvents 1

HCID 69303m-Tolyl isocyanateSolvent

Procedure

The process is performed in a similar manner to that described in Example 1, but starting with 0.34 g of tert-butyl (2S,4S,5R)-3-(2-aminoacetyl)-5-methoxycarbonyl-4-(2-fluorophenyl)-2-thiazolidinecarboxylate dissolved in 10 ml of tetrahydrofuran and 106 μl of 3-methylphenyl isocyanate. The crude product is purified by chromatography on silica [eluent: ethyl acetate/cyclohexane (20/80 by volume)]. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure at 40° C. After beating in diisopropyl ether, 0.17 g of tert-butyl (2S,4S,5R)-5-methoxycarbonyl-3-{2-[3-(3-methylphenyl)ureido]acetyl}-4-(2-fluorophenyl)-2-thiazolidinecarboxylate is thus obtained in the form of a pale yellow foam, Rf=0.30, [ethyl/acetate cyclohexane (30/70 by volume); 1H NMR (250 MHz, (CD3)2SO, at a temperature of 363 K, δ in ppm): 1.53 (s, 9H: CH3 of the tert-butyl); 2.27 (s, 3H: ARCH3); 3.34 (s, 3H: COOCH3); from 3.60 to 3.80 and 4.06 (mt and dd respectively (J=17 and 5 Hz), 1H each: COCH2N); 4.33 (d, J=3 Hz, 1H: H at C5 of the ring); 5.74 (mt, 1H: H at C2 of the ring); 6.01 (d, J=3 Hz, 1H: H at C4 of the ring); 6.23 (t, J=5 Hz, 1H NHCO); 6.78 (broad d, J=7.5 Hz, 1H: aromatic H (H ortho to the CH3)); 7.09 (t, J=7.5 Hz, 1H: aromatic H (H meta to the CH3)); from 7.10 to 7.50 (mt, 5H: aromatic H); 8.03 (mt, 1H: aromatic H (H meta to the F)); 8.40 (s, 1H: ArNHCO).

Workup

  1. customThe crude product is purified by chromatography on silica [eluent: ethyl acetate/cyclohexane (20/80 by volume)]
  2. additionThe fractions containing the expected product
  3. concentrationconcentrated to dryness under reduced pressure at 40° C

Sources & evidence

ORD record
ord-db7f5299c843435eaac7fe97a865a655
Source dataset
uspto-grants-1997_11
Patent number
US05686622

Reaction notes

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