Trifluoroacetic acid → HCID 58641227, Verbindung

HRID 1394947Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1394947
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12](C(OC(C)(C)C)=O)[C@H:11]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:10]=1.FC(F)(F)C(O)=O.[C:34]([O:38][C:39]([NH:41][C@H:42]([C:49](O)=[O:50])[C:43]([CH3:48])([CH3:47])[C:44]([OH:46])=[O:45])=[O:40])([CH3:37])([CH3:36])[CH3:35].Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(CC)CC)C>ClCCl>[C:34]([O:38][C:39]([NH:41][C@H:42]([C:49]([N:12]1[CH2:13][C:9]([C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[F:1])=[CH:10][C@H:11]1[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:50])[C:43]([CH3:48])([CH3:47])[C:44]([OH:46])=[O:45])=[O:40])([CH3:36])([CH3:37])[CH3:35]

Komponenten

8

Edukt 6

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58641236HCID 58641236, VerbindungHCID 86605057HCID 86605057, Verbindung

Produkt 1

HCID 58641227HCID 58641227, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of tert-butyl(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate (5-5, 1.00 g, 2.80 mmol, 1 equiv) in a 4:1 mixture of dichloromethane and trifluoroacetic acid (20 mL) was stirred for 30 minutes, then concentrated. The residue was dried via benzene azeotrope (1×50 mL), then dissolved in DMF (30 mL). N-(tert-butoxycarbonyl)-3,3-dimethylaspartic acid (29-3, 1.08 g, 4.20 mmol, 1.50 equiv), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 0.805 g, 4.20 mmol, 1.50 equiv), 1-hydroxy-7-azabenzotriazole (0.571 g, 4.20 mmol, 1.50 equiv) and triethylamine (2.73 mL, 19.6 mmol, 7.00 equiv) were added, and the resulting mixture was stirred at 23° C. for 20 hours. The reaction mixture was partitioned between water, acidified to pH 2, and ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography through silica gel (hexane initially, grading to 100% EtOAc) followed by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present) to provide (3S)-3-[(tert-butoxycarbonyl)amino]4-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2,2-dimethyl-4-oxobutanoic acid (29-4) as a white foam. 1H NMR (500 M CDCl3) major rotamer: δ 7.28 (m, 5H), 7.05 (m, 3H), 6.40 (s, 1H), 5.89 (br s, 1H), 5.74 (d, 1H, J=10.2 Hz), 5.17 (d, 1H, J=14.2 Hz), 4.93 (ddd, 1H, J=13.9, 4.4, 1.7 Hz), 4.62 (d, 1H, J=10.2 Hz), 1.45 (s, 9H), 1.30 (s, 3H), 1.05 (s, 3H). LRMS m/z (M+H) 501.5 found, 501.2 required.

Aufarbeitung

  1. concentrationconcentrated
  2. dry with materialThe residue was dried via benzene
  3. dissolutiondissolved in DMF (30 mL)
  4. stirringthe resulting mixture was stirred at 23° C. for 20 hours
  5. customThe reaction mixture was partitioned between water
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography through silica gel (hexane initially

Quellen und Nachweise

ORD-Eintrag
ord-5ce3cf704cba4993acb5d19d1cf69533
Quelldatensatz
uspto-grants-2008_03
Patentnummer
US07348440B2

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