Hydrochloric Acid → (S)-2-(4-Chloroindolin-1-yl)-4-hydroxy-N-(4-(N-thiazol-2-ylsulfamoyl)phenyl)butanamide

HRID 2043187Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2043187
C[Al](C)C.[CH:5]1[C:10]([NH2:11])=[CH:9][CH:8]=[C:7]([S:12]([NH:15][C:16]2[S:20][CH:19]=[CH:18][N:17]=2)(=[O:14])=[O:13])[CH:6]=1.[Cl:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:23]=1[CH2:24][CH2:25][N:26]2[C@H:31]1[CH2:35][CH2:34][O:33][C:32]1=[O:36].Cl>CCCCCC.ClCCl.C(OC(=O)C)C>[Cl:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:23]=1[CH2:24][CH2:25][N:26]2[C@@H:31]([CH2:35][CH2:34][OH:33])[C:32]([NH:11][C:10]1[CH:5]=[CH:6][C:7]([S:12](=[O:14])(=[O:13])[NH:15][C:16]2[S:20][CH:19]=[CH:18][N:17]=2)=[CH:8][CH:9]=1)=[O:36]

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 5340SulfathiazoleHCID 16682925TrimethylaluminumHCID 59465791HCID 59465791, Verbindung

Produkt 1

HCID 59465758(S)-2-(4-Chloroindolin-1-yl)-4-hydroxy-N-(4-(N-thiazol-2-ylsulfamoyl)phenyl)butanamideAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6344DichloromethaneLösungsmittel2×HCID 8058HexaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Prepared using general procedure 58. Under an N2 atmosphere at RT, 2M-trimethyl aluminium in hexane (9.13 mL) was added dropwise to a stirring solution of sulfathiazole (4.6 g, 18.27 mmol) in dichloromethane (100 mL) in 30 minutes. Upon completion of addition, the mixture was stirred at RT for an hour. Added (S)-3-(4-chloroindolin-1-yl)dihydrofuran-2(3H)-one (3.56 g, 14.97 mmol) in dichloromethane (20 mL) to above solution over 30 minutes. The mixture was stirred for 16 hrs at RT. The reaction mixture was diluted with 500 mL of ethylacetate were added. The aqueous phase was acidified to pH 2 with an (1N) aqueous HCl solution. The ethyl acetate layer was washed with (1N) aqueous HCl (3×200 mL) till LCMS showed disappearance of sulfathiazole. The organic layer was dried over MgSO4, filtered, concentrated. Purification via silica gel chromatography using 2-10% methanol in dichloromethane gave the amide as a white solid (5.9 g, 80% yield). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=493.2; tR=1.46 min. 1H NMR (400 MHz, DMSO) δ 12.69 (s, 1H), 7.74 (s, 4H), 7.24 (d, J=4.6 Hz, 1H), 6.98 (t, J=8.0 Hz, 1H), 6.81 (d, J=4.5 Hz, 1H), 6.56-6.54 (m, 2H), 4.71 (t, J=4.8 Hz, 1H), 4.43-4.39 (m, 1H), 3.79 (q, J=9.3 Hz, 1H), 3.64-3.58 (m, 2H), 3.51-3.48 (m, 1H), 3.17 (d, J=5.2 Hz, 1H), 3.00-2.89 (m, 1H), 1.93 (dd, J=6.0, 13.5 Hz, 1H), 1.88 (s, 1H).

Aufarbeitung

  1. customPrepared
  2. additionUpon completion of addition
  3. stirringThe mixture was stirred for 16 hrs at RT
  4. additionwere added
  5. washThe ethyl acetate layer was washed with (1N) aqueous HCl (3×200 mL) till LCMS
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification via silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-7ab2acbc56f149719c70de612f71cf90
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08586589B2

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