Cyclobutanone → HCID 16048990, compound

HRID 1364167Notes

Reaction equation

HRID 1364167 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH:23]=[C:22]4[C:16]([CH2:17][CH2:18][N:19]([C:24](OC(C)(C)C)=O)[CH2:20][CH2:21]4)=[N:15]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:31]1(=O)[CH2:34]C[CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>FC(F)(F)C(O)=O.CO.ClCCl>[CH:24]1([N:19]2[CH2:20][CH2:21][C:22]3=[CH:23][N:14]([CH:11]4[CH2:10][CH2:9][N:8]([C:5]5[CH:6]=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=5)[CH2:13][CH2:12]4)[N:15]=[C:16]3[CH2:17][CH2:18]2)[CH2:34][CH2:31][CH2:32]1

Participants

7

Reactant 3

HCID 14496Cyclobutanone3×HCID 5049666Sodium triacetoxyborohydride3×HCID 66931012HCID 66931012, compound

Product 1

HCID 16048990HCID 16048990, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent4×HCID 6422Trifluoroacetic acidSolvent

Procedure

1,1-Dimethylethyl 2-[1-(6-methyl-3-pyridinyl)-4-piperidinyl]-4,5,7,8-tetrahydropyrazolo[3,4-d]azepine-6(2H)-carboxylate (may be prepared as described in Description 50) (27 mg, 0.065 mmol) was stirred in trifluoroacetic acid (0.5 ml)/dichloromethane (1 ml) for 2 hours. Mixture was then diluted with methanol and passed through an SCX cartridge. A mixture of the product in dichloromethane (1.3 ml) was treated with cyclobutanone (0.010 ml, 0.13 mmol) followed by sodium triacetoxyborohydride (28 mg, 0.13 mmol) (about 5 min later). The resulting mixture was then stirred under Argon for 17.25 h. After an additional 1.25 hours, more dichloromethane (2.5 ml), cyclobutanone (0.030 ml) and then sodium triacetoxyborohydride (28 mg) were added and the mixture stirred for an additional 3.75 hours and then for an additional 2.5 hours. After a further 1 hour, more cyclobutanone (0.030 ml) followed by sodium triacetoxyborohydride (2 eq) were added and the resulting mixture left at room temperature under Ar for 16.75 hours. Then dichloromethane (2 ml) was added. Methanol was then added and the mixture purified by SCX eluting with methanol and then methanol/ammonia (2M). This material was purified by Mass Directed Autopreparation to give a product which was purified further by SCX eluting with methanol and then methanol/2M NH3 in methanol to afford the title compound (E44).

Workup

  1. customabout 5 min
  2. waitAfter an additional 1.25 hours
  3. stirringthe mixture stirred for an additional 3.75 hours
  4. waitfor an additional 2.5 hours
  5. waitAfter a further 1 hour
  6. additionwere added
  7. waitthe resulting mixture left at room temperature under Ar for 16.75 hours
  8. customthe mixture purified by SCX
  9. washeluting with methanol
  10. customThis material was purified by Mass Directed Autopreparation
  11. customto give a product which
  12. customwas purified further by SCX
  13. washeluting with methanol

Sources & evidence

ORD record
ord-c63216082b434fa4af3910170b6a8248
Source dataset
uspto-grants-2011_02
Patent number
US07888347B2

Reaction notes

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