Binap, (A+-)- → HCID 66931012, compound

HRID 1364139Notes

Reaction equation

HRID 1364139 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH:16]=[C:15]3[C:9]([CH2:10][CH2:11][N:12]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:14]3)=[N:8]2)[CH2:3][CH2:2]1.Br[C:25]1[CH:26]=[CH:27][C:28]([CH3:31])=[N:29][CH:30]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:31][C:28]1[N:29]=[CH:30][C:25]([N:1]2[CH2:6][CH2:5][CH:4]([N:7]3[CH:16]=[C:15]4[C:9]([CH2:10][CH2:11][N:12]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:14]4)=[N:8]3)[CH2:3][CH2:2]2)=[CH:26][CH:27]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-2×HCID 12010205-Bromo-2-methylpyridine2×HCID 23676156Sodium t-butoxide2×HCID 66930855HCID 66930855, compound

Product 1

HCID 66931012HCID 66931012, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

1,1-Dimethylethyl 2-(4-piperidinyl)-4,5,7,8-tetrahydropyrazolo[3,4-d]azepine-6(2H)-carboxylate (may be prepared as described in Description 49) (65 mg, 0.21 mmol), 5-bromo-2-methylpyridine (52 mg, 0.30 mmol), palladium acetate (5 mg, 0.02 mmol), (+/−) BINAP (25 mg, 0.04 mmol), sodium tert-butoxide (39 mg, 0.041 mmol) and dioxane (2 ml) were mixed and heated to reflux under Argon and kept at this temperature for 14 h. After an additional 1.5 h, more 5-bromo-2-methylpyridine (1.5 eq), palladium acetate (0.1 eq), (+/−) BINAP (0.2 eq) and sodium tert-butoxide (2 eq) were added and the mixture stirred at reflux under Argon for an additional 7 h. the mixture was then allowed to cool over 45 mins and was then diluted with methanol and purified by SCX eluting with methanol, then 2M methanol/NH3. Purified further by SPE(Si) eluting with dichloromethane:methanol 50:1→25:1→10:1. Further purification by Mass Directed Autopreparation afforded the title compound (D50). MS (ES+) m/e 412 [M+H]+.

Workup

  1. temperatureheated
  2. temperatureto reflux under Argon
  3. waitAfter an additional 1.5 h
  4. temperatureat reflux under Argon for an additional 7 h. the mixture
  5. temperatureto cool over 45 mins
  6. custompurified by SCX
  7. washeluting with methanol
  8. customPurified further by SPE(Si) eluting with dichloromethane:methanol 50:1→25:1→10:1
  9. customFurther purification by Mass Directed Autopreparation

Sources & evidence

ORD record
ord-136a2d4b1f27421dbfbd89b4d2dd1489
Source dataset
uspto-grants-2011_02
Patent number
US07888347B2

Reaction notes

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