Hydrochloric Acid → (S)-5-(4-(1-(2-(3-(difluoromethyl)-4,4,7,7-tetrafluoro-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetamido)-2-(3,5-difluorophenyl)ethyl)-2-(4-oxopiperidin-1-yl)pyrimidin-5-yl)-2-fluorobenzamide

HRID 2170342Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2170342
[F:1][CH:2]([F:56])[C:3]1[C:11]2[C:10]([F:13])([F:12])[CH2:9][CH2:8][C:7]([F:15])([F:14])[C:6]=2[N:5]([CH2:16][C:17]([NH:19][C@H:20]([C:30]2[C:35]([C:36]3[CH:37]=[CH:38][C:39]([F:45])=[C:40]([CH:44]=3)[C:41]([NH2:43])=[O:42])=[CH:34][N:33]=[C:32]([N:46]3[CH2:55][CH2:54][C:49]4(OCC[O:50]4)[CH2:48][CH2:47]3)[N:31]=2)[CH2:21][C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[CH:23]=2)=[O:18])[N:4]=1.Cl>C1COCC1>[F:56][CH:2]([F:1])[C:3]1[C:11]2[C:10]([F:12])([F:13])[CH2:9][CH2:8][C:7]([F:14])([F:15])[C:6]=2[N:5]([CH2:16][C:17]([NH:19][C@H:20]([C:30]2[C:35]([C:36]3[CH:37]=[CH:38][C:39]([F:45])=[C:40]([CH:44]=3)[C:41]([NH2:43])=[O:42])=[CH:34][N:33]=[C:32]([N:46]3[CH2:47][CH2:48][C:49](=[O:50])[CH2:54][CH2:55]3)[N:31]=2)[CH2:21][C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[CH:23]=2)=[O:18])[N:4]=1

Komponenten

4

Edukt 2

HCID 313Hydrochloric AcidHCID 90281363(S)-5-(4-(1-(2-(3-(difluoromethyl)-4,4,7,7-tetrafluoro-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetamido)-2-(3,5-difluorophenyl)ethyl)-2-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)pyrimidin-5-yl)-2-fluorobenzamide

Produkt 1

HCID 90281442(S)-5-(4-(1-(2-(3-(difluoromethyl)-4,4,7,7-tetrafluoro-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetamido)-2-(3,5-difluorophenyl)ethyl)-2-(4-oxopiperidin-1-yl)pyrimidin-5-yl)-2-fluorobenzamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Compound 19B (40 mg, 0.05 mmol) was dissolved in 2 mL of THF and to it was added 1 mL of 6N HCl. The mixtures was stirred at ambient temperature for 16 hours and then extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase HPLC eluting with acetonitrile/water (with 0.1% TFA) to afford the title compound. 1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H), 7.71 (d, J=5.0 Hz, 1H), 7.46 (s, 1H), 7.33 (m, 1H), 7.30-7.18 (m, 1H), 7.11 (d, J=11.0 Hz, 1H), 6.98 (m, 1H), 6.78 (t, J=53.6 Hz, 1H), 6.58 (m, 1H), 6.20 (d, J=6.2 Hz, 2H), 5.37 (d, J=7.4 Hz, 1H), 5.11-4.89 (m, 2H), 4.22-3.98 (m, 4H), 2.83 (m, 2H), 2.54 (m, 8H). MS (m/z) 754.11 [M+H]+.

Aufarbeitung

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by reverse phase HPLC
  8. washeluting with acetonitrile/water (with 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-465e6e4a5f5b426d987d75a72a2f6721
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09050344B2

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