1-Hydroxybenzotriazole → methyl 4-[(2S,4S)-1-[4-[N'-(2-chlorophenyl)ureido]-3-methoxyphenylacetyl]-4-methoxy-2-pyrrolidinyl]methoxybenzoate

HRID 350494Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 350494
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:23])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([OH:20])=O)=[CH:13][C:12]=1[O:21][CH3:22].[CH3:24][O:25][C@@H:26]1[CH2:30][NH:29][C@H:28]([CH2:31][O:32][C:33]2[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][CH:34]=2)[CH2:27]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:23])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([N:29]2[CH2:30][C@@H:26]([O:25][CH3:24])[CH2:27][C@H:28]2[CH2:31][O:32][C:33]2[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][CH:34]=2)=[O:20])=[CH:13][C:12]=1[O:21][CH3:22]

Komponenten

6

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16093585methyl 4-[(2S,4S)-4-methoxy-2-pyrrolidinyl]methoxybenzoateHCID 235118674-[N'-(2-chlorophenyl)ureido]-3-methoxyphenylacetic acid

Produkt 1

HCID 69333168methyl 4-[(2S,4S)-1-[4-[N'-(2-chlorophenyl)ureido]-3-methoxyphenylacetyl]-4-methoxy-2-pyrrolidinyl]methoxybenzoateAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 4-[N′-(2-chlorophenyl)ureido]-3-methoxyphenylacetic acid (398 mg, 1.19 mmol), methyl 4-[(2S,4S)-4-methoxy-2-pyrrolidinyl]methoxybenzoate (317 mg, 1.19 mmol), EDC.HCl (342 mg, 1.79 mmol), HOBT (242 mg, 1.79 mmol) and Et3 N (0.83 ml, 5.95 mmol) in DMF (5 ml) was stirred at room temperature for 13 h. The mixture was poured into ice water and extracted with EtOAc. The combined extracts were washed with ice water and brine. After dried over Na2SO4, the extracts were concentrated in vacuo. The residue was chromatographed on silica gel [50 g, CHCl3/Aectone (10/1)CHCl3/MeOH (20/1)], to give methyl 4-[(2S,4S)-1-[4-[N′-(2-chlorophenyl)ureido]-3-methoxyphenylacetyl]-4-methoxy-2-pyrrolidinyl]methoxybenzoate (600 mg, 87%) as a colorless amorphous solid 1H-NMR (CDCl3) δ 1.99–2.06 (m, 1H), 2.34 (d, J=13.9 Hz, 1H), 3.30 (s, 3H), 3.59 (d, J=7.4 Hz, 1H), 3.62 (d, J=3.2 Hz, 2H), 3.83 (s, 3H), 3.88 (s, 3H), 4.00–4.18 (m, 3H), 4.42–4.51 (m, 2H), 6.82–7.07 (m, 7H), 7.28 (d, J=8.3 Hz, 1H), 7.35 (dd, J=7.9, 1.5 Hz, 1H), 7.94–8.00 (m, 3H), 8.18(d, J=8.3 Hz, 1H); MS (ESI) m/z 582 (M++1), 584 (M++3).

Aufarbeitung

  1. extractionextracted with EtOAc
  2. washThe combined extracts were washed with ice water and brine
  3. dry with materialAfter dried over Na2SO4
  4. concentrationthe extracts were concentrated in vacuo
  5. customThe residue was chromatographed on silica gel [50 g, CHCl3/Aectone (10/1)CHCl3/MeOH (20/1)]

Quellen und Nachweise

ORD-Eintrag
ord-df643472273c4cef98b76263e6750ed7
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07179819B2

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