Trifluoroacetic acid → N-[(1R,6R)-6-Amino-2,2-difluorocyclohexyl]-4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophene-2-carboxamide

HRID 1842609Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1842609
C(OC(=O)[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][C:10]([F:15])([F:14])[C@@H:9]1[NH:16][C:17]([C:19]1[S:20][C:21]([CH3:37])=[C:22]([C:24]2[CH:25]=[N:26][N:27]3[CH:32]=[C:31]([O:33][CH:34]([F:36])[F:35])[CH:30]=[N:29][C:28]=23)[CH:23]=1)=[O:18])(C)(C)C.FC(F)(F)C(O)=O>ClCCl.[OH-].[Na+]>[NH2:7][C@H:8]1[C@@H:9]([NH:16][C:17]([C:19]2[S:20][C:21]([CH3:37])=[C:22]([C:24]3[CH:25]=[N:26][N:27]4[CH:32]=[C:31]([O:33][CH:34]([F:35])[F:36])[CH:30]=[N:29][C:28]=34)[CH:23]=2)=[O:18])[C:10]([F:14])([F:15])[CH2:11][CH2:12][CH2:13]1

Komponenten

5

Edukt 2

HCID 6422Trifluoroacetic acidHCID 89750994tert-Butyl{(1R,2R)-2-[({4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamate

Produkt 1

HCID 86692126N-[(1R,6R)-6-Amino-2,2-difluorocyclohexyl]-4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophene-2-carboxamideAusbeute 50,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 14798Sodium HydroxideLösungsmittel

Versuchsvorschrift

tert-Butyl{(1R,2R)-2-[({4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamate (0.900 g, 1.61 mmol) was dissolved in dichloromethane (8 mL) and trifluoroacetic acid (1.50 mL, 19.5 mmol) added. The reaction was stirred at room temperature for 16 h. After deprotection was complete, the mixture was diluted with 1N NaOH. The aqueous layer was extracted 3× with dichloromethane. The organic layers were combined, dried with sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (0-16% MeOH/DCM) to give the title compound (0.371 g, 0.811 mmol). LRMS (APCI) calc'd for (C19H19F4N5O2S) [M+H]+, 458.1; found 458.0. 1H NMR (CDCl3, 500 MHz) δ 8.66 (d, J=2.5, 1H), 8.48 (d, J=2.5, 1H), 8.26 (s, 1H), 7.92 (s, 1H), 7.06 (d, J=8.8, 1H), 6.61 (t, J=71.5, 1H), 4.45 (m, 1H), 3.32 (m, 1H), 2.57 (s, 3H), 2.17 (m, J=8.6, 1H), 1.47-1.92 (m, 5H).

Aufarbeitung

  1. extractionThe aqueous layer was extracted 3× with dichloromethane
  2. dry with materialdried with sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography (0-16% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-fc013c79a300418a9e14d410be896551
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946237B2

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