Ethyl 2-amino-2-methylpropanoate hydrochloride → 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-5,5-dimethylimidazolidine-2,4-dione

HRID 658778

반응식

HRID 658778 반응식
CC1C(CN2C=C(C(N=[N+]=[N-])=O)C=N2)=C(C)ON=1.[N:19]([C:22]1[CH:23]=[N:24][N:25]([CH2:27][C:28]2[C:29]([CH3:34])=[N:30][O:31][C:32]=2[CH3:33])[CH:26]=1)=[C:20]=[O:21].Cl.[NH2:36][C:37]([CH3:44])([CH3:43])[C:38](OCC)=[O:39]>C1(C)C=CC=CC=1>[CH3:34][C:29]1[C:28]([CH2:27][N:25]2[CH:26]=[C:22]([N:19]3[C:38](=[O:39])[C:37]([CH3:44])([CH3:43])[NH:36][C:20]3=[O:21])[CH:23]=[N:24]2)=[C:32]([CH3:33])[O:31][N:30]=1

참가 물질

5

반응물 3

HCID 22343822Ethyl 2-amino-2-methylpropanoate hydrochlorideHCID 574224251-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazole-4-carbonyl azide2회HCID 584095734-((4-isocyanato-1H-pyrazol-1-yl)methyl)-3,5-dimethylisoxazole

생성물 1

HCID 595243883-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-5,5-dimethylimidazolidine-2,4-dione수율 65%

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

온도
50 °C

실험 절차

1-((3,5-dimethylisoxazol-4-yl) methyl)-1H-pyrazole-4-carbonyl azide (Example 10-1a) (10 g, 41.0 mmol) is stirred under nitrogen in dry toluene (150 mL) along with molecular sieves at reflux until no emission of nitrogen was observed, which indicates complete conversion of 1-((3,5-dimethylisoxazol-4-yl) methyl)-1H-pyrazole-4-carbonyl azide into 4-((4-isocyanato-1H-pyrazol-1-yl)methyl)-3,5-dimethylisoxazole. The solution was cooled down to 50° C. and ethyl 2-amino-2-methylpropanoate hydrochloride (5.30 g, 41.0 mmol) was added in one portion. Stirring continued for 3 hours at 50° C. followed by reflux for 12 hours. The mixture was filtered over a pad of celite. The filtrate was concentrated on the rotovap and the residue was purified over silica gel using 25% ethyl acetate in hexanes. Yield 65% (8.00 g), white solid. 1H NMR (DMSO-d6, 400 MHz): □s, 6H), 2.15 (s, 3H), 2.41 (s, 3H), 5.18 (s, 2H), 7.78 (d, J=0.4 Hz, 1H), 8.16 (d, J=0.4 Hz, 1H), 8.59 (br s, 1H). MS 304 (MH+). This compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 2.27 μM.

후처리

  1. temperatureat reflux until no emission of nitrogen
  2. temperatureby reflux for 12 hours
  3. filtrationThe mixture was filtered over a pad of celite
  4. concentrationThe filtrate was concentrated on the rotovap
  5. customthe residue was purified over silica gel using 25% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-6236a0ffadf94fda8f740651fd2c1960
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08076491B2

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