Acetone → HCID 16048989, compound

HRID 1364166Notes

Reaction equation

HRID 1364166 reaction equation
Cl.[CH3:2][CH:3]([N:5]1[CH2:11][CH2:10][C:9]2=[CH:12][N:13]([C:15]3[CH:16]=[CH:17][C:18]([N:21]4[CH2:25][CH2:24][CH2:23][C:22]4=[O:26])=[N:19][CH:20]=3)[N:14]=[C:8]2[CH2:7][CH2:6]1)[CH3:4].N1N(C2C=CC(N3CCCC3=O)=NC=2)C=C2CCNCCC=12.CC(C)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CO>[CH3:22][OH:26].[NH3:5].[CH3:4][CH:3]([N:5]1[CH2:11][CH2:10][C:9]2=[CH:12][N:13]([C:15]3[CH:16]=[CH:17][C:18]([N:21]4[CH2:25][CH2:24][CH2:23][C:22]4=[O:26])=[N:19][CH:20]=3)[N:14]=[C:8]2[CH2:7][CH2:6]1)[CH3:2]

Participants

8

Reactant 4

HCID 180Acetone2×HCID 5049666Sodium triacetoxyborohydride2×HCID 66930803HCID 66930803, compoundHCID 66930846HCID 66930846, compound

Product 2

HCID 16048989HCID 16048989, compoundHCID 21705897Ammonia methanol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1-[5-(5,6,7,8-tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl)-2-pyridinyl]-2-pyrrolidinone (may be prepared as described in Description 19) (37 mg, 0.12 mmol) in dichloromethane (2.5 ml) was treated with acetone (0.018 ml, 0.25 mmol) and then stirred under Argon for 20 min and then treated with sodium triacetoxyborohydride (53 mg, 0.25 mmol) and the resulting mixture stirred under Argon at room temperature for 16.5 hours. 2 hours later, more acetone (2 eq) was then added, followed 5 min later by more sodium triacetoxyborohydride (2 eq) and the mixture stirred under Argon at room temperature for 5 hours. The mixture was then diluted with methanol and then purified by SCX eluting with methanol and then 2M ammonia in methanol to give a 73:27 (by LCMS DAD) 88:12 (by LCMS ELSD) mixture of 1-{5-[6-(1-methylethyl)-5,6,7,8-tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl]-2-pyridinyl}-2-pyrrolidinone hydrochloride (E43) and 1-[5-(5,6,7,8-tetrahydropyrazolo[3,4-d]azepin-2(4H)-yl)-2-pyridinyl]-2-pyrrolidinone (D19) (33 mg). A solution of this mixture in dichloromethane (2.5 ml) was treated with acetone (0.018 ml, 0.25 mmol) under Argon and the mixture stirred for 2-3 min at room temperature. Sodium triacetoxyborohydride (53 mg, 0.25 mmol) was then added and the mixture stirred under Argon at room temperature for 15.75 hours. After an additional 1 hour, more acetone (5 eq) was added followed 5 min later by more sodium triacetoxyborohydride and the mixture stirred at room temperature under Argon for an additional 7.75 h. The mixture was then diluted with methanol and purified by SCX eluting with methanol then methanol/NH3 (2M). Purified further by SPE (Si) eluting with dichloromethane:methanol 50:1→25:1→10:1→5:1→2:1. Purified further by Mass Directed Autopreparation followed by SCX eluting with methanol then methanol/NH3 (2M) to afford the title product (E43).

Workup

  1. stirringthe mixture stirred under Argon at room temperature for 15.75 hours
  2. waitAfter an additional 1 hour
  3. stirringthe mixture stirred at room temperature under Argon for an additional 7.75 h
  4. custompurified by SCX
  5. washeluting with methanol
  6. customPurified further by SPE (Si)
  7. washeluting with dichloromethane:methanol 50:1→25:1→10:1→5:1→2:1
  8. customPurified further by Mass Directed Autopreparation
  9. washeluting with methanol

Sources & evidence

ORD record
ord-4d1996b963214569ac4cbeed637cf84b
Source dataset
uspto-grants-2011_02
Patent number
US07888347B2

Reaction notes

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