Nortropine → Methyl 4-(3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)-5-phenyl-thieno[2,3-d]pyrimidine-6-carboxylate

HRID 928596Notes

Reaction equation

HRID 928596 reaction equation
Cl[C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[C:9]([C:17]([O:19][CH3:20])=[O:18])[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.CCN(C(C)C)C(C)C.[CH2:30]1[C@H:36]2[NH:37][C@H:32]([CH2:33][CH:34]([OH:38])[CH2:35]2)[CH2:31]1>C1COCC1.O>[OH:38][CH:34]1[CH2:33][CH:32]2[N:37]([C:2]3[C:3]4[C:10]([C:11]5[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=5)=[C:9]([C:17]([O:19][CH3:20])=[O:18])[S:8][C:4]=4[N:5]=[CH:6][N:7]=3)[CH:36]([CH2:30][CH2:31]2)[CH2:35]1

Participants

6

Reactant 3

HCID 73480NortropineHCID 81531DiisopropylethylamineHCID 89579551Methyl 4-chloro-5-phenyl-thieno[2,3-d]pyrimidine-6-carboxylate

Product 1

HCID 89579774Methyl 4-(3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)-5-phenyl-thieno[2,3-d]pyrimidine-6-carboxylateYield 44%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 4-chloro-5-phenyl-thieno[2,3-d]pyrimidine-6-carboxylate (3.231 g, 10.59 mmol) and DIPEA (2.39 mL, 15.89 mmol) in THF (60 mL) at room temperature was added nortropine (1.682 g, 15.89 mmol) and the reaction left to stir overnight. The reaction was diluted with water (60 mL) and the layers separated. The aqueous layer was acidified to pH 3 and extracted repeatedly with 3:1 chloroform/IPA. The combined organic layers were dried over sodium sulphate, filtered and concentrated under reduced pressure to afford methyl 4-(3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)-5-phenyl-thieno[2,3-d]pyrimidine-6-carboxylate (1.839 g, 44%). LCMS: Rt=4.23, 396 (M+1).

Workup

  1. waitthe reaction left
  2. customthe layers separated
  3. extractionextracted repeatedly with 3:1 chloroform/IPA
  4. dry with materialThe combined organic layers were dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6a81934fef6f46c993be37d6c36a9650
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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