Methanol → HCID 89579740, compound

HRID 928590Notes

Reaction equation

HRID 928590 reaction equation
[CH:1]([NH2:4])([CH3:3])[CH3:2].[C:5]1([C:11]2[C:19]3[C:18]([N:20]4[CH:25]5[CH2:26][CH2:27][CH:21]4[CH2:22][C:23](=O)[CH2:24]5)=[N:17][CH:16]=[N:15][C:14]=3[S:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CO>C(Cl)Cl>[CH:1]([NH:4][CH:23]1[CH2:22][CH:21]2[N:20]([C:18]3[C:19]4[C:11]([C:5]5[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=5)=[CH:12][S:13][C:14]=4[N:15]=[CH:16][N:17]=3)[CH:25]([CH2:26][CH2:27]2)[CH2:24]1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 6363Isopropylamine3×HCID 5049666Sodium triacetoxyborohydride3×HCID 89579938HCID 89579938, compound

Product 1

HCID 89579740HCID 89579740, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Isopropylamine (0.0385 mL, 0.4472 mmol) was added to a solution of 8-(5-phenylthieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-one (0.05 g, 0.1491 mmol) in DCM (2 mL). Sodium triacetoxyborohydride (0.1663 g, 0.7454 mmol) was added and the mixture was stirred at room temperature overnight. A second batch of isopropylamine (0.0385 mL, 0.4472 mmol) and sodium triacetoxyborohydride (0.1663 g, 0.7454 mmol) was added and the mixture was stirred overnight. A third batch of isopropylamine (0.0385 mL, 0.4472 mmol) and sodium triacetoxyborohydride (0.1663 g, 0.7454 mmol) was added and the mixture was stirred over three nights. Methanol (2 mL) was added to quench the reaction. The solvent was evaporated and the residue was dissolved in dichloromethane (2 mL) and water (2 mL). The layers were separated and the aqueous was extracted with dichloromethane (2×2 mL). The combined organic layers were evaporated to give a colourless oil. Mass: 77 mg. This was purified by silica chromatography (10 g cartridge; eluent dichloromethane/0.5 M ammonia in methanol 0 to 10%; all output collected). Fractions containing the target compound (by TLC and LCMS; broad peak) were combined and evaporated to give N-isopropyl-8-(5-phenylthieno[2,3-d]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-3-amine a white solid. (19 mg). LCMS RT=3.04 min. M+1=379.

Workup

  1. stirringthe mixture was stirred overnight
  2. stirringthe mixture was stirred over three nights
  3. customto quench
  4. customthe reaction
  5. customThe solvent was evaporated
  6. dissolutionthe residue was dissolved in dichloromethane (2 mL)
  7. customThe layers were separated
  8. extractionthe aqueous was extracted with dichloromethane (2×2 mL)
  9. customThe combined organic layers were evaporated
  10. customto give a colourless oil
  11. customThis was purified by silica chromatography (10 g cartridge
  12. customall output collected)
  13. additionFractions containing the target compound (by TLC and LCMS; broad peak)
  14. customevaporated

Sources & evidence

ORD record
ord-9ada7e65db584a73a0289c06fe79e9c0
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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