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Hydrochloric Acid → methyl {5-[4-(4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]bicyclo[3.2.2]non-1-yl}acetate

HRID 2353081
ノート
印刷プレビュー

反応式

HRID 2353081 の反応式
Br[C:2]([CH3:26])([CH3:25])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]23[CH2:19][CH2:18][C:15]([CH2:20][C:21]([O:23][CH3:24])=[O:22])([CH2:16][CH2:17]2)[CH2:14][CH2:13][CH2:12]3)=[CH:7][CH:6]=1)=O.[NH2:27][C:28]1[C:29]([OH:35])=[N:30][CH:31]=[N:32][C:33]=1[NH2:34].Cl>CCO>[NH2:34][C:33]1[C:28]2[N:27]=[C:3]([C:5]3[CH:10]=[CH:9][C:8]([C:11]45[CH2:19][CH2:18][C:15]([CH2:20][C:21]([O:23][CH3:24])=[O:22])([CH2:16][CH2:17]4)[CH2:14][CH2:13][CH2:12]5)=[CH:7][CH:6]=3)[C:2]([CH3:26])([CH3:25])[O:35][C:29]=2[N:30]=[CH:31][N:32]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 25258351Methyl {5-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[3.2.2]non-1-yl}acetate2 回HCID 178508814HCID 178508814、化合物

生成物 1

HCID 25258354methyl {5-[4-(4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]bicyclo[3.2.2]non-1-yl}acetate収率 65%

試薬・触媒・溶媒 1

HCID 702
Ethanol
溶媒

反応条件

温度
80 °C

実験手順

To a solution of methyl {5-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[3.2.2]non-1-yl}acetate (Intermediate 24; 80 mg, 0.19 mmol) in absolute EtOH (20 mL) was added 5,6-diaminopyrimidin-4-ol (30 mg, 0.21 mmol) followed by 1M HCl (0.21 mL). The suspension was heated under gentle reflux (80° C.) overnight then allowed to cool, the solvent removed and the residue treated with 2M NaOH (2 mL). The aqueous phase was extracted into EtOAc (3×50mL), the organic extracts were combined, dried (MgSO4) and concentrated to leave a pale yellow gum. This was purified on a 12 g Crawford silicycle cartridge, loading in DCM and eluting with 0-5-10% MeOH-DCM, giving the title compound as a pale yellow gum (55 mg, 0.123 mmol, 65%); 1H NMR (CDCl3) 1.41-1.61 (14H, m), 1.71 (6H, s), 2.07 (2H, s), 3.61 (3H, s), 7.11 (2H, d), 7.51 (2H, d), 8.14 (1H, s); MS m/e MH+ 449.

後処理

  1. temperatureThe suspension was heated
  2. temperatureto cool
  3. customthe solvent removed
  4. additionthe residue treated with 2M NaOH (2 mL)
  5. extractionThe aqueous phase was extracted into EtOAc (3×50mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customto leave a pale yellow gum
  9. customThis was purified on a 12 g Crawford silicycle cartridge, loading in DCM
  10. washeluting with 0-5-10% MeOH-DCM

出典と根拠

ORDレコード
ord-5248102baae0449e8b44ad002676299c
出典データセット
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07749997B2

反応ノート

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