Water → Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(4-fluoro-3-methylphenylamino)nicotinate

HRID 2092755

Reaktionsgleichung

Reaktionsgleichung von HRID 2092755
Cl[C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[C:17]([CH3:22])[CH:16]=2)[N:3]=1.CCN(CC)CC.[NH2:30][C@@H:31]1[CH2:36][CH2:35][CH2:34][CH2:33][C@@H:32]1[NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41].O>C1COCC1.CCOC(C)=O>[C:40]([O:39][C:38]([NH:37][C@H:32]1[CH2:33][CH2:34][CH2:35][CH2:36][C@H:31]1[NH:30][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[C:17]([CH3:22])[CH:16]=2)[N:3]=1)=[O:44])([CH3:43])([CH3:41])[CH3:42]

Komponenten

7

Edukt 4

HCID 962WaterHCID 8471TriethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 58317541Methyl 6-chloro-4-cyano-2-(4-fluoro-3-methylphenylamino)nicotinate

Produkt 1

HCID 67237937Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(4-fluoro-3-methylphenylamino)nicotinateAusbeute 12,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of methyl 6-chloro-4-cyano-2-(4-fluoro-3-methylphenylamino)nicotinate (390 mg, 1.220 mmol), Et3N (0.204 mL, 1.464 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (392 mg, 1.830 mmol) in THF (5 mL) was stirred at 80° C. overnight. Water and EtOAc were subsequently added to the mixture and the aqueous phase was extracted with EtOAc. The organic phases were combined, washed with H2O and brine, dried over MgSO4, and evaporated. The residue was diluted with EtOAc and filtered to give the title compound as a yellow solid (75 mg, 12.36%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.03-1.71 (m, 17H), 2.22 (d, J=0.98 Hz, 3H), 3.80-3.82 (m, 3H), 3.83 (br s, 1H), 4.01-4.09 (m, 1H), 6.48 (s, 1H), 6.62 (d, J=7.81 Hz, 1H), 7.06 (t, J=9.03, 1H), 7.39 (d, J=4.39 Hz, 1H), 7.50-7.68 (m, 1H), 10.41 (br s, 1H).

Aufarbeitung

  1. extractionthe aqueous phase was extracted with EtOAc
  2. washwashed with H2O and brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. additionThe residue was diluted with EtOAc
  6. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-17d1eb55aab74e47896f15f6395603d6
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08440689B2

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