Tetrahydro-4H-pyran-4-one → 8-Chloro-1-(3,4,5,6-tetrahydro-2h-[1,2']bipyridinyl-4-yl)-5-(tetrahydro-pyran-4-yl)-5,6-dihydro-4h-2,3,5,10b-tetraaza-benzo[e]azulene

HRID 1243575Notes

Reaction equation

HRID 1243575 reaction equation
[O:1]1[CH2:6][CH2:5][C:4](=O)[CH2:3][CH2:2]1.[Cl:8][C:9]1[CH:34]=[CH:33][C:12]2[N:13]3[C:17]([CH2:18][NH:19][CH2:20][C:11]=2[CH:10]=1)=[N:16][N:15]=[C:14]3[CH:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)[CH2:23][CH2:22]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:8][C:9]1[CH:34]=[CH:33][C:12]2[N:13]3[C:17]([CH2:18][N:19]([CH:4]4[CH2:5][CH2:6][O:1][CH2:2][CH2:3]4)[CH2:20][C:11]=2[CH:10]=1)=[N:16][N:15]=[C:14]3[CH:21]1[CH2:22][CH2:23][N:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)[CH2:25][CH2:26]1

Participants

5

Reactant 3

HCID 121599Tetrahydro-4H-pyran-4-one2×HCID 5049666Sodium triacetoxyborohydride2×HCID 113264888-Chloro-1-(3,4,5,6-tetrahydro-2h-[1,2']bipyridinyl-4-yl)-5,6-dihydro4h-2,3,5,10b-tetraaza-benzo[e]azulene

Product 1

HCID 219255668-Chloro-1-(3,4,5,6-tetrahydro-2h-[1,2']bipyridinyl-4-yl)-5-(tetrahydro-pyran-4-yl)-5,6-dihydro-4h-2,3,5,10b-tetraaza-benzo[e]azuleneYield 50.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

Tetrahydro-pyran-4-one (68 mg, 0.68 mmol) was added to a solution of the amine of example 4 (130 mg, 0.34 mmol) in dichloromethane (5 ml). The mixture was stirred at room temperature for 0.25 hours before sodium triacetoxyborohydride (217 mg, 1.0 mmol) was added, and the reaction mixture was stirred for a further 18 hours. Further tetrahydro-pyran-4-one (68 mg, 0.68 mmol) and sodium triacetoxyborohydride (217 mg, 1.0 mmol) were added and the reaction mixture was heated to 40° C. for 24 hours. The reaction mixture was partitioned between 2N aqueous sodium carbonate solution (10 ml) and ethyl acetate (50 ml). The organic layer was washed three times with 2N aqueous sodium carbonate solution (10 ml), once with saturated aqueous brine, and then dried over magnesium sulphate before filtering and evaporating the filtrate under reduced pressure. The residue was purified by chromatography on silica gel using a gradient of ethyl acetate in pentane (0% to 30%) as eluant, followed by chromatography on silica gel using a gradient of methanol in dichloromethane (0% to 5%) as eluant, to afford the title compound as a brown foam (80 mg).

Workup

  1. additionwas added
  2. customThe reaction mixture was partitioned between 2N aqueous sodium carbonate solution (10 ml) and ethyl acetate (50 ml)
  3. washThe organic layer was washed three times with 2N aqueous sodium carbonate solution (10 ml)
  4. dry with materialonce with saturated aqueous brine, and then dried over magnesium sulphate
  5. filtrationbefore filtering
  6. customevaporating the filtrate under reduced pressure
  7. customThe residue was purified by chromatography on silica gel using a gradient of ethyl acetate in pentane (0% to 30%) as eluant

Sources & evidence

ORD record
ord-47c32d0be63a446ba2de309b7edeee1f
Source dataset
uspto-grants-2006_10
Patent number
US07119088B2

Reaction notes

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