Hydrochloric Acid → AZD 8329

HRID 552615노트

반응식

HRID 552615 반응식
Cl.O.[NH:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][CH:6]=1)[NH2:4].[CH:14]12[CH2:23][CH:18]3[CH2:19][CH:20]([CH2:22][CH:16]([CH2:17]3)[CH:15]1[NH:24][C:25](=[O:37])[C:26](=[CH:33]N(C)C)[C:27](=O)[C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:21]2>CO>[CH:16]12[CH2:22][CH:20]3[CH2:19][CH:18]([CH2:23][CH:14]([CH2:21]3)[CH:15]1[NH:24][C:25]([C:26]1[CH:33]=[N:4][N:3]([C:5]3[CH:6]=[CH:7][C:8]([C:9]([OH:11])=[O:10])=[CH:12][CH:13]=3)[C:27]=1[C:28]([CH3:31])([CH3:30])[CH3:29])=[O:37])[CH2:17]2

참가 물질

6

반응물 4

HCID 313Hydrochloric Acid2회HCID 962Water2회HCID 120894-Hydrazinobenzoic acidHCID 72312260HCID 72312260, 화합물2회

생성물 1

HCID 25006684AZD 8329수율 74.1%

시약·촉매·용매 1

HCID 887Methanol용매2회

반응 조건

온도
22.5 °C

실험 절차

Hydrochloric acid (34.5% w/w, 15.88 g, 5.48 g @100.0%, 0.1504 mole, 1.0 mol. eq) and water (70 ml, 1.4 rel. vol) were added to a suspension of 4-hydrazinobenzoic acid (23.35 g, 22.88 g @100.0%, 0.1504 mole, 1.0 mol. eq) in methanol (1250 ml, 12.5 rel. vol). The resulting suspension was stirred for 30 min at 20 to 25° C. and a solution of N-(2-adamantyl)-2-(dimethylaminomethylidene)-4,4-dimethyl-3-oxo-pentanamide (intermediate #4) (53.47 g, 50.0 g @100.0%, 0.150 in 4 mole, 1.0 mol. eq) at 20-25° C. in methanol (250 ml, 5.0 rel. vol)] added over a period of 20 minutes followed by hydrochloric acid (34.5% w/w, 2.38 g, 0.82 g @100.0%, 0.02264 mole, 0.15 mol. eq) and water (70.0 ml, 1.4 rel. vol). The reaction mass temperature was increased to 62-65° C. and maintained for 90.0 min. For work up methanol solution was concentrated atmospherically until the residual volume 6.0 rel. vol (300.0 ml) remained. The resulting suspension was cooled to 20-25° C. and stirred for 1.0 hr. The product was filtered and washed with ethyl acetate (200.0 ml, 4.0 rel. vol) and sucked dry for 30 min. The product was dried under vacuum (100 mbar) at 50° C. for 8 hrs to give crude 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic acid (47.0 g, 73.0%).

후처리

  1. temperatureThe reaction mass temperature was increased to 62-65° C.
  2. temperaturemaintained for 90.0 min
  3. concentrationFor work up methanol solution was concentrated atmospherically until the residual volume 6.0 rel
  4. temperatureThe resulting suspension was cooled to 20-25° C.
  5. stirringstirred for 1.0 hr
  6. filtrationThe product was filtered
  7. washwashed with ethyl acetate (200.0 ml, 4.0 rel. vol)
  8. customsucked dry for 30 min
  9. customThe product was dried under vacuum (100 mbar) at 50° C. for 8 hrs

출처 및 근거

ORD 기록
ord-61aa6bc533514ae8a2491bc850923a70
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07951833B2

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