Potassium trimethylsilanolate → 2-[4-(4-{4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl}phenyl)bicyclo[2.2.2]octan-1-yl]propanoic acid

HRID 2353075노트

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HRID 2353075 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]([CH:26]([CH3:31])[C:27]([O:29]C)=[O:28])([CH2:22][CH2:23]4)[CH2:20][CH2:19]5)=[CH:14][CH:13]=3)[C:8]([CH3:33])([CH3:32])[O:7][C:6]=2[N:5]=[CH:4][N:3]=1.C[Si](C)(C)[O-].[K+]>C1COCC1.CS(C)=O.CC#N.O>[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]([CH:26]([CH3:31])[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])([CH3:33])[O:7][C:6]=2[N:5]=[CH:4][N:3]=1

참가 물질

5

반응물 2

HCID 23668039Potassium trimethylsilanolateHCID 25258353methyl 2-{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}propanoate2회

생성물 1

HCID 250161682-[4-(4-{4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl}phenyl)bicyclo[2.2.2]octan-1-yl]propanoic acid수율 21.2%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 86584666DMSO MeCN water용매

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온도
100 °C

실험 절차

A mixture of methyl 2-{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}propanoate (Intermediate 18; 220 mg, 0.49 mmol) and potassium trimethylsilanolate (315 mg, 2.45 mmol) in THF (5 mL) was heated in a microwave for 35 mins at 100° C. and was then stirred at ambient temperature for 2 days. The solvent was removed under reduced pressure and the residue partitioned between 2M HCl (20 mL) and EtOAc (50 mL) and the aqueous phase was further extracted with EtOAc (50 mL). The organic extracts were combined, dried (MgSO4) and concentrated to leave a gum. This was dissolved in DMSO/MeCN/H2O (7:2:1) and separated by reverse phase chromatography eluting 5-95% water-acetonitrile 0.2% TFA, providing the title compound (45 mg, 0.104 mmol, 21%) as a white solid; 1H NMR δ 1.01 (d, 3H), 1.49-1.55 (m, 3H), 1.62 (s, 6H), 1.64-1.69 (m, 3H), 1.78-1.81 (m, 6H), 2.12 (q, 1H), 7.05 (s, 1H), 7.40 (d, 2H), 7.65 (d, 2H), 7.99 (s, 1H); MS m/e MH+ 435.

후처리

  1. customThe solvent was removed under reduced pressure
  2. customthe residue partitioned between 2M HCl (20 mL) and EtOAc (50 mL)
  3. extractionthe aqueous phase was further extracted with EtOAc (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customto leave a gum
  7. customseparated by reverse phase chromatography
  8. washeluting 5-95% water-acetonitrile 0.2% TFA

출처 및 근거

ORD 기록
ord-bb2fc71328144a479b72e6331583d6b8
출처 데이터셋
uspto-grants-2010_07
특허 번호
US07749997B2

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