Ammonium Chloride → tert-butyl ((1S,4S)-4-(2-cyclopropyl-2-hydroxyethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

HRID 1747127Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1747127
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[O:6]=[CH:7][CH2:8][C@@:9]1([C:22]([N:24]2[CH2:33][CH2:32][C:31]3[N:30]=[CH:29][C:28]([C:34]([F:37])([F:36])[F:35])=[CH:27][C:26]=3[CH2:25]2)=[O:23])[CH2:13][C@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH:11]=[CH:10]1.[NH4+].[Cl-]>C1COCC1>[CH:1]1([CH:7]([OH:6])[CH2:8][C@@:9]2([C:22]([N:24]3[CH2:33][CH2:32][C:31]4[N:30]=[CH:29][C:28]([C:34]([F:35])([F:36])[F:37])=[CH:27][C:26]=4[CH2:25]3)=[O:23])[CH2:13][C@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH:11]=[CH:10]2)[CH2:3][CH2:2]1

Komponenten

5

Edukt 3

HCID 25517Ammonium ChlorideHCID 86708134tert-butyl ((1S,4S)-4-(2-oxoethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamateHCID 178418630HCID 178418630, Verbindung

Produkt 1

HCID 86708135tert-butyl ((1S,4S)-4-(2-cyclopropyl-2-hydroxyethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

To a solution of cyclopropyl magnesium bromide (6.88 mL of a 0.5 M solution in THF, 3.44 mmol, 8 eq) in THF (5 mL) at 0° C. under Ar was added a solution of the product of Step A (195 mg, 0.43 mmol, 1 eq) in THF (17 mL) dropwise over 30 min. After 45 min, saturated NH4Cl was added, the solution extracted with ethyl acetate, the organics combined, dried over MgSO4 and concentrated. Purification by chromatography (12 g column) eluting with 30 to 100% EtOAc/heptane afforded the title compound of Step B as a mix of diastereomers. 1H NMR (CHLOROFORM-d) δ: 8.70 (br. s., 1H), 7.70 (br. s., 1H), 6.11-6.42 (m, 1H), 5.77 (t, J=5.1 Hz, 1H), 4.81 (d, J=12.2 Hz, 4H), 4.03 (dt, J=12.8, 6.2 Hz, 1H), 3.81-3.98 (m, 1H), 3.59-3.75 (m, 2H), 3.03-3.25 (m, 2H), 2.69-3.00 (m, 2H), 2.19-2.67 (m, 3H), 1.91-2.18 (m, 3H), 1.55-1.88 (m, 5H), 1.42 (s, 9H), 0.88-0.99 (m, 1H), 0.42-0.56 (m, 2H), 0.14-0.35 (m, 2H). Calculated for C25H32F3N3O4: 496.2 (M+1). found: 496.2.

Aufarbeitung

  1. extractionthe solution extracted with ethyl acetate
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customPurification by chromatography (12 g column)
  5. washeluting with 30 to 100% EtOAc/heptane

Quellen und Nachweise

ORD-Eintrag
ord-bc819346354d4653a8b6366aaaaaf187
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09150532B2

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