Acetic Acid → HCID 86658256, Verbindung

HRID 1040160Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1040160
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:37])[CH2:30][CH2:29][C@H:28]([C:31]([O:33][CH3:34])=[O:32])[C:27]([CH3:36])([CH3:35])[CH2:26]3)=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1.[O-:38][C:39]#[N:40].[K+].C(O)(=O)C.O>C1COCC1>[C:39]([NH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:37])[CH2:30][CH2:29][C@H:28]([C:31]([OH:33])=[O:32])[C:27]([CH3:35])([CH3:36])[CH2:26]3)=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:17])([F:19])[F:18])[CH:13]=[CH:12][N:11]=2)[CH:8]=1)(=[O:38])[NH2:40].[C:39]([NH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[S:24][C:23]([C@@:25]3([OH:37])[CH2:30][CH2:29][C@H:28]([C:31]([O:33][CH3:34])=[O:32])[C:27]([CH3:35])([CH3:36])[CH2:26]3)=[N:22][CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:18])([F:19])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1)(=[O:38])[NH2:40]

Komponenten

7

Edukt 4

HCID 176Acetic AcidHCID 962WaterHCID 11378442Potassium cyanateHCID 67432750HCID 67432750, Verbindung

Produkt 2

HCID 67430374HCID 67430374, VerbindungHCID 86658256HCID 86658256, VerbindungAusbeute 184,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of methyl(1S,4R)-4-{5-[3-(aminomethyl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (40 mg, 0.075 mmol) in anhydrous THF (1.5 ml) was added potassium cyanate (12.12 mg, 0.149 mmol, 2.0 equiv), acetic acid (8.55 μl, 0.149 mmol, 2.0 equiv), and water (4.5 ml). The mixture was stirred at 50° C. for 14 h. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted with EtOAc (40 ml). The organic layer were dried over Na2SO4, filtered and concentrated to provide the desired product, methyl (1S,4R)-4-[5-(3-[(carbarnoylamino)methyl]-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (40 mg, 88%), as an orange oil. MS ESI: [M+H]+ m/z 579.2. 1H NMR (500 MHz, DMSO) δ 10.3 (s, 1H), 8.83 (d, J=4.9 Hz, 1H), 8.03 (bs, 1H), 7.88 (s, 1H), 7.50 (s, 1H), 7.28 (d, 1H, J=4.9 Hz), 7.17 (s, 1H), 6.46 (m, 1H), 5.55 (s, 2H), 4.16 (m, 2H), 3.59 (s, 3H), 2.31 (m, 1H), 1.87-1.84 (m, 4H), 1.75-1.73 (m, 2H), 1.17 (s, 3H), 0.96 (s, 3H).

Aufarbeitung

  1. customThe reaction mixture was quenched with saturated aqueous NaHCO3
  2. extractionextracted with EtOAc (40 ml)
  3. dry with materialThe organic layer were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-bf3f94020c884f3d9b6206ef0726bb2d
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08551984B2

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