Hydrochloric Acid → 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

HRID 908115노트

반응식

HRID 908115 반응식
[NH2:1][C:2]1[C:3]([OH:9])=[N:4][CH:5]=[N:6][C:7]=1[NH2:8].Cl.Br[C:12]([CH3:35])([CH3:34])[C:13]([C:15]1[CH:20]=[CH:19][C:18]([C:21]23[CH2:28][CH2:27][C:24]([CH2:29][C:30]([O:32][CH3:33])=[O:31])([CH2:25][CH2:26]2)[CH2:23][CH2:22]3)=[CH:17][CH:16]=1)=O>O.C(O)C>[NH2:8][C:7]1[C:2]2[N:1]=[C:13]([C:15]3[CH:16]=[CH:17][C:18]([C:21]45[CH2:28][CH2:27][C:24]([CH2:29][C:30]([O:32][CH3:33])=[O:31])([CH2:25][CH2:26]4)[CH2:23][CH2:22]5)=[CH:19][CH:20]=3)[C:12]([CH3:35])([CH3:34])[O:9][C:3]=2[N:4]=[CH:5][N:6]=1

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 25258107Methyl {4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate2회HCID 178508814HCID 178508814, 화합물

생성물 1

HCID 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}acetate수율 64.2%

시약·촉매·용매 2

HCID 702Ethanol용매2회HCID 962Water용매

반응 조건

온도
100 °C

실험 절차

To a solution of 5,6-diaminopyrimidin-4-ol (280 mg, 2.2 mmol) in water (8 mL), absolute ethanol (25 mL) and 1M HCl (2.2 mL, 2.2 mmol) was added a solution of methyl {4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate (Intermediate 9; 877 mg, 2.15 mmol) in absolute EtOH (80 mL). The solution was heated to 100° C. overnight then allowed to cool to ambient temperature, evaporated to dryness, and the residue treated with 2M NaOH to adjust the pH to 10. The resulting suspension was filtered to provide a yellow solid which was purified on a 12 g presearch silica cartridge dry loading on silica (2 g) and eluting with 0-2.5-5% MeOH-DCM to provide the title compound as a white solid (601 mg, 1.38 mmol, 64%)1H NMR δ 1.59-1.63 (12H, m), 1.79-1.83 (6H, m), 2.16 (2H, s), 3.59 (3H, s), 6.91 (2H, s), 7.39 (2H, d), 7.64 (2H, d), 7.95 (1H, s); MS m/e MH+ 435.

후처리

  1. temperatureto cool to ambient temperature
  2. customevaporated to dryness
  3. additionthe residue treated with 2M NaOH
  4. filtrationThe resulting suspension was filtered
  5. customto provide a yellow solid which
  6. customwas purified on a 12 g presearch silica cartridge
  7. customdry loading on silica (2 g)
  8. washeluting with 0-2.5-5% MeOH-DCM

출처 및 근거

ORD 기록
ord-c809db5ba6d84ee78d5892c48f3cbccb
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08017603B2

반응 노트

불러오는 중…