Sodium Hydroxide → (4-(4-(4-Amino-7,7-dimethyl-7H-pyrimido(4,5-b)(1,4)oxazin-6-yl)phenyl)bicyclo(2.2.2)oct-1-yl)acetic Acid

HRID 908104노트

반응식

HRID 908104 반응식
[NH2:1][C:2]1[C:11]2[N:10]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([C:18]45[CH2:25][CH2:24][C:21]([CH2:26][C:27]([O:29]C)=[O:28])([CH2:22][CH2:23]4)[CH2:20][CH2:19]5)=[CH:14][CH:13]=3)[C:8]([CH3:32])([CH3:31])[O:7][C:6]=2[N:5]=[CH:4][N:3]=1.[OH-].[Na+]>CO.C1COCC1>[NH2:1][C:2]1[C:11]2[N:10]=[C:9]([C:12]3[CH:13]=[CH:14][C:15]([C:18]45[CH2:23][CH2:22][C:21]([CH2:26][C:27]([OH:29])=[O:28])([CH2:20][CH2:19]4)[CH2:24][CH2:25]5)=[CH:16][CH:17]=3)[C:8]([CH3:32])([CH3:31])[O:7][C:6]=2[N:5]=[CH:4][N:3]=1

참가 물질

5

반응물 2

HCID 14798Sodium Hydroxide2회HCID 25258352methyl {4-[4-(4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate

생성물 1

HCID 16202164(4-(4-(4-Amino-7,7-dimethyl-7H-pyrimido(4,5-b)(1,4)oxazin-6-yl)phenyl)bicyclo(2.2.2)oct-1-yl)acetic Acid

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of methyl {4-[4-(4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate (122 mg, 0.28 mmol) in MeOH (10 mL) and THF (5 mL) was added 2M NaOH (0.7 mL). The reaction mixture was stirred at ambient temperature overnight then further 2M NaOH (0.7 mL) was added and the reaction mixture heated to 50° C. for 5 hrs. The mixture was allowed to cool, the solvent was removed under reduced pressure and the residue was acidified to pH 2 with 2M HCl and the suspension filtered and dried. The product was purified on a basic reverse phase preparative HPLC system loading in NMP (˜2 mL), water (˜2 mL) and 1-2 drops of 0.88 ammonia, and eluting with 13-40% water (+1% NH3)-MeCN, to provide the title compound as a solid, 40 mg (0.0952 mmol, 34%).

후처리

  1. temperaturethe reaction mixture heated to 50° C. for 5 hrs
  2. temperatureto cool
  3. customthe solvent was removed under reduced pressure
  4. filtrationthe suspension filtered
  5. customdried
  6. customThe product was purified on a basic reverse phase preparative HPLC system loading in NMP (˜2 mL)
  7. washwater (˜2 mL) and 1-2 drops of 0.88 ammonia, and eluting with 13-40% water (+1% NH3)-MeCN

출처 및 근거

ORD 기록
ord-f7ef373b44a74fe8aadbd3d130207629
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08017603B2

반응 노트

불러오는 중…