Trifluoroacetic acid → (2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-N-methyl-pyrrolidine-2-carboxamide

HRID 908433Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 908433
C(O)(C(F)(F)F)=O.[NH2:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH:16]=[N:17][N:18]([C@H:20]3[CH2:24][N:23](C(OC(C)(C)C)=O)[C@H:22]([C:32](=[O:35])[NH:33][CH3:34])[CH2:21]3)[CH:19]=2)=[CH:11][C:10]=1[C:36]1[O:37][C:38]2[CH:44]=[CH:43][CH:42]=[CH:41][C:39]=2[N:40]=1>>[NH2:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH:16]=[N:17][N:18]([C@H:20]3[CH2:24][NH:23][C@H:22]([C:32]([NH:33][CH3:34])=[O:35])[CH2:21]3)[CH:19]=2)=[CH:11][C:10]=1[C:36]1[O:37][C:38]2[CH:44]=[CH:43][CH:42]=[CH:41][C:39]=2[N:40]=1

Komponenten

3

Edukt 2

HCID 6422Trifluoroacetic acidHCID 67388909(2S,4R)-tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-2-(methylcarbamoyl)pyrrolidine-1-carboxylate

Produkt 1

HCID 57687107(2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-N-methyl-pyrrolidine-2-carboxamide

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

TFA (5 ml) was added to (2S,4R)-tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-2-(methylcarbamoyl)pyrrolidine-1-carboxylate under argon. The resulting solution was stirred at 25° C. for 1 hour. The solution was evaporated under reduced pressure, adsorbed with ammonia in methanol solution. The crude product was purified by flash chromatography on silica gel eluting with 1 to 6% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness to afford (2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-N-methyl-pyrrolidine-2-carboxamide (38 mg) as a pale yellow solid. 37% Aqueous formaldehyde (8.42 μl) at 0° C. was added to a stirred solution 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-N-methyl-pyrrolidine-2-carboxamide (38 mg) dissolved in methanol (2 ml) and dichloromethane (2 ml) over a period of 5 minutes under argon. The resulting solution was stirred at 0° C. for 5 minutes. Sodium triacetoxyhydroborate (23.96 mg, 0.11 mmol) was added and the mixture was stirred 5 minutes at 25° C. A solution of ammonia in methanol 7N (1 ml) was added and the mixture was adsorbed on silica gel. The crude product was purified by flash chromatography on silica gel eluting with 1 to 6% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness to afford (2S,4R)-4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazol-1-yl]-N,1-dimethyl-pyrrolidine-2-carboxamide (30 mg) after overnight stirring in acetonitrile as a solid. NMR Spectrum: (DMSOd6) 2.23-2.32 (m, 1H), 2.35 (s, 3H), 2.47-2.56 (m partially hidden by DMSOd5, 1H), 2.65 (d, 3H), 2.76-2.84 (m, 1H), 3.19-3.27 (m, 1H), 3.47-3.56 (m, 1H), 4.89-4.99 (m, 1H), 7.41-7.50 (m, 2H), 7.67 (bs, 2H), 7.77-7.82 (m, 1H), 7.83-7.87 (m, 1H), 7.90 (q, 1H), 7.97 (s, 1H), 8.37 (s, 1H), 8.44 (d, 1H), 8.53 (d, 1H) Mass spectrum: M+H+ 418

Aufarbeitung

  1. customThe solution was evaporated under reduced pressure
  2. customThe crude product was purified by flash chromatography on silica gel eluting with 1 to 6% methanolic ammonia (7 N) in dichloromethane
  3. customThe solvent was evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-1d2a8787b7bd4c77b796ec23eab39ac1
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08017611B2

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