Hydrochloric Acid → N-{(1R,2R)-2-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-2,2,2-trifluoro-acetamide

HRID 1687213Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1687213
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[NH:15][C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])[C:5]([Cl:22])=[CH:4][N:3]=1.[CH2:23]([N:25]1[CH2:31][CH2:30][C:29]2[CH:32]=[C:33]([NH2:36])[CH:34]=[CH:35][C:28]=2[CH2:27][CH2:26]1)[CH3:24].Cl.C(=O)([O-])[O-]>COCCO.O1CCOCC1>[Cl:22][C:5]1[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[NH:15][C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])=[N:7][C:2]([NH:36][C:33]2[CH:34]=[CH:35][C:28]3[CH2:27][CH2:26][N:25]([CH2:23][CH3:24])[CH2:31][CH2:30][C:29]=3[CH:32]=2)=[N:3][CH:4]=1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 19660Carbonate IonHCID 189434013-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamineHCID 86633893HCID 86633893, Verbindung

Produkt 1

HCID 56663171N-{(1R,2R)-2-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-2,2,2-trifluoro-acetamideAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 80192-MethoxyethanolLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-2,2,2-trifluoro-acetamide (204 mg, 0.571 mmol) was added into a Vial, followed by a solution of 3-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (106 mg, 0.557 mmol) in 2-Methoxyethanol (7 mL). 4 M of Hydrogen chloride in 1,4-Dioxane (0.2 mL) was added and the reaction was heated at 120° C. After 7 h, the reaction was cooled to room temperature, Macroporous carbonate resin (3.16 mmol/g loading; 530 mg, 1.68 mmol) was added and stirred 30 min. The polymer was filtered off, and the solvent removed in vacuo. The residue was dissolved in DCM, then chromatographed (2×12 g SiO2, ISCO, 0-10% MeOH:DCM) to afford N-{(1R,2R)-2-[5-Chloro-2-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-2,2,2-trifluoro-acetamide (128 mg, 45%) as a beige solid. m.p.=165° C.; LCMS (m/e) 511 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.98 (s, 1H), 7.94 (s, 1H), 7.32 (m, 2H), 7.08 (d, 1H, J=8.1 Hz), 6.93 (s, 1H), 5.27 (d, 1H, J=7.4 Hz), 3.99 (m, 1H), 3.87 (m, 1H), 3.68 (m, 3H), 3.11 (m, 2H), 2.7-2.9 (m, 4H), 2.30 (d, 1H, J=11.4 Hz), 2.16 (d, 1H, J=11.7 Hz), 1.8-1.9 (m, 2H), 1.2-1.6 (m, 8H).

Aufarbeitung

  1. temperaturethe reaction was cooled to room temperature
  2. filtrationThe polymer was filtered off
  3. customthe solvent removed in vacuo
  4. dissolutionThe residue was dissolved in DCM
  5. customchromatographed (2×12 g SiO2, ISCO, 0-10% MeOH:DCM)

Quellen und Nachweise

ORD-Eintrag
ord-ffafac5be6374d8c87cc95f997f10ba7
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08148391B2

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