Acetone → 4-[6-(1-Methylethyl)-5,6,7,8-tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl]benzonitrile

HRID 1364160Notes

Reaction equation

HRID 1364160 reaction equation
[N:1]1[N:2]([C:11]2[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=2)[CH:3]=[C:4]2[CH2:10][CH2:9][NH:8][CH2:7][CH2:6][C:5]=12.[CH3:19][C:20]([CH3:22])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CO>ClCCl.C(O)(=O)C>[CH3:19][CH:20]([N:8]1[CH2:9][CH2:10][C:4]2=[CH:3][N:2]([C:11]3[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=3)[N:1]=[C:5]2[CH2:6][CH2:7]1)[CH3:22]

Participants

7

Reactant 4

HCID 180Acetone2×HCID 887MethanolHCID 5049666Sodium triacetoxyborohydride2×HCID 669308824-(5,6,7,8-Tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl)benzonitrile

Product 1

HCID 160489134-[6-(1-Methylethyl)-5,6,7,8-tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl]benzonitrile

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent

Procedure

4-(5,6,7,8-Tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl)benzonitrile (may be prepared as described in Description 11) (assumed 0.148 mmol) was dissolved in dichloromethane (2 ml) and acetic acid (2 drops). Acetone (16 μl, 0.22 mmol) and sodium triacetoxyborohydride (47 mg, 0.22 mmol) were added and the mixture stirred at room temperature for 2 hours. Further aliquots of acetone (32 μl, 0.44 mmol) and sodium triacetoxyborohydride (47 mg, 0.22 mmol) were added and stirring continued for a further 70 hours. Methanol was added and the solution poured onto a 2 g SCX column which was eluted with methanol then 2M ammonia in methanol. The basic fractions were evaporated and the residue purified by flash chromatography eluting with 0-5% 2M ammonia in methanol/dichloromethane to afford the title compound (E34).

Workup

  1. stirringstirring
  2. waitcontinued for a further 70 hours
  3. additionthe solution poured onto a 2 g SCX column which
  4. washwas eluted with methanol
  5. customThe basic fractions were evaporated
  6. customthe residue purified by flash chromatography
  7. washeluting with 0-5% 2M ammonia in methanol/dichloromethane

Sources & evidence

ORD record
ord-ec0486c7d65443618ed1c9457a79373e
Source dataset
uspto-grants-2011_02
Patent number
US07888347B2

Reaction notes

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