Sodium Hydroxide → AZD 8329

HRID 1799373노트

반응식

HRID 1799373 반응식
[OH-].[Na+].[CH:3]12[CH2:12][CH:7]3[CH2:8][CH:9]([CH2:11][CH:5]([CH2:6]3)[CH:4]1[NH:13][C:14]([C:16]1[CH:17]=[N:18][N:19]([C:25]3[CH:34]=[CH:33][C:28]([C:29]([O:31]C)=[O:30])=[CH:27][CH:26]=3)[C:20]=1[C:21]([CH3:24])([CH3:23])[CH3:22])=[O:15])[CH2:10]2>CO>[CH:3]12[CH2:10][CH:9]3[CH2:8][CH:7]([CH2:6][CH:5]([CH2:11]3)[CH:4]1[NH:13][C:14]([C:16]1[CH:17]=[N:18][N:19]([C:25]3[CH:34]=[CH:33][C:28]([C:29]([OH:31])=[O:30])=[CH:27][CH:26]=3)[C:20]=1[C:21]([CH3:23])([CH3:24])[CH3:22])=[O:15])[CH2:12]2

참가 물질

4

반응물 2

HCID 14798Sodium HydroxideHCID 59516081HCID 59516081, 화합물2회

생성물 1

HCID 25006684AZD 8329수율 80%

시약·촉매·용매 1

HCID 887Methanol용매

반응 조건

온도
62.5 °C

실험 절차

Aqueous sodium hydroxide (2M) (2.5 eq) was added portionwise over 5 minutes to a stirred suspension of methyl 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoate (Intermediate #56) (1.0 eq) in methanol (10 vol) at 20° C. (exotherm 20-27° C.). The resulting suspension was heated to 70° C. (jacket temperature), (batch refluxes approx 60-65° C.) for 1 hour (complete by LCMS). The orange reaction mixture was cooled to 20° C. (solution remained slightly cloudy) and filtered through celite to remove a small amount of solids. The filtrate was then poured into a flange flask and water (25 vol) was added. The mixture was then adjusted to pH 3 with 2M HCl (approx 800-850 ml) (turns very thick). The aqueous was then filtered and the pale yellow solid washed with water, sucked dry overnight, and washed with acetonitrile and finally 1:1 acetonotrile/diethyl ether and dried under vacuum at 50° C. for 72 hours (weekend) to give 4-[4-(2-adamantylcarbamoyl)-5-tertbutyl-pyrazol-1-yl]benzoic acid (80%) as a solid.

후처리

  1. temperatureThe orange reaction mixture was cooled to 20° C. (solution
  2. filtrationfiltered through celite
  3. customto remove a small amount of solids
  4. additionThe filtrate was then poured into a flange flask
  5. additionwater (25 vol) was added
  6. filtrationThe aqueous was then filtered
  7. washthe pale yellow solid washed with water
  8. customsucked dry overnight
  9. washwashed with acetonitrile and finally 1:1 acetonotrile/diethyl ether
  10. customdried under vacuum at 50° C. for 72 hours (weekend)

출처 및 근거

ORD 기록
ord-4c55537e5c684dd4aae7e40eb53d2b04
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08344016B2

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