Morpholine → HCID 58641332, Verbindung

HRID 1394962Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1394962
[CH:1]1([C@H:4]([NH:26][CH2:27][CH2:28][C:29](OC)=[O:30])[C:5]([N:7]2[CH2:11][C:10]([C:12]3[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=3[F:19])=[CH:9][C@H:8]2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:6])[CH2:3][CH2:2]1.[OH-].[Na+].[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1>CC(O)(C)C.CN(C=O)C>[CH:1]1([C@H:4]([NH:26][CH2:27][CH2:28][C:29]([N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)=[O:30])[C:5]([N:7]2[CH2:11][C:10]([C:12]3[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=3[F:19])=[CH:9][C@H:8]2[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:6])[CH2:3][CH2:2]1

Komponenten

8

Edukt 5

HCID 8083MorpholineHCID 14798Sodium HydroxideHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58641201HCID 58641201, Verbindung

Produkt 1

HCID 58641332HCID 58641332, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6386tert-ButanolLösungsmittel

Versuchsvorschrift

A solution of methyl N-{(1S)-1-cyclopropyl-2-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-oxoethyl}-β-alaninate (40-1, 84 mg, 0.19 mmol, 1 equiv) and sodium hydroxide (1N, 0.57 mL, 0.57 mmol, 3.00 equiv) in t-BuOH (4 mL) was stirred at 23 deg C. for 4 h. The reaction mixture was concentrated and the residue was partitioned between brine adjusted to pH 4 with aqueous 1 N HCL solution and ethyl acetate (2×40 mL). The combined organic layers were dried over sodium sulfate and concentrated. A solution of the residue, morpholine (0.083 mL, 0.95 mmol, 5.0 equiv), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 73 mg, 0.38 mmol, 2.0 equiv), and 1-hydroxy-7-azabenzotriazole (52 mg, 0.38 mmol, 2.0 equiv) in DMF (2 mL) was heated at 50° C. for 20 h. The reaction mixture was partitioned between aqueous saturated sodium bicarbonate solution and ethyl acetate (2×30 mL). The combined organic layers were dried over sodium sulfate and were concentrated. The residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present) and the desired fractions partitioned between saturated sodium bicarbonate solution and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated to provide N-{(1S)-1-cyclopropyl-2-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-oxoethyl}-3-morpholin-4-yl-3-oxopropan-1-amine (41-2) as a white foam. LRMS m/z M+H) 496.5 found, 496.2 required.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was partitioned between brine
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe reaction mixture was partitioned between aqueous saturated sodium bicarbonate solution and ethyl acetate (2×30 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationwere concentrated
  8. customThe residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present)
  9. customthe desired fractions partitioned between saturated sodium bicarbonate solution and ethyl acetate
  10. dry with materialThe organic layer was dried over sodium sulfate
  11. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-977e3dde7098486abfaa8065b6063bcc
Quelldatensatz
uspto-grants-2008_03
Patentnummer
US07348440B2

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