Methanol → HCID 68154041, compound

HRID 341075Notes

Reaction equation

HRID 341075 reaction equation
[O:1]=[C:2]1[C:6]2=[CH:7][N:8]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH:26]=[CH:25][CH:24]=[N:23]4)=[CH:18][CH:17]=3)[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[C:5]2=[N:4][N:3]1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH2:33][C:34](OC)=[O:35].[BH4-].[Li+].CO.[Cl-].[NH4+].ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.C(=O)(O)[O-].[Na+]>C(OCC)C.ClCCl.O>[OH:35][CH2:34][CH2:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[N:3]1[C:2](=[O:1])[C:6]2=[CH:7][N:8]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH:26]=[CH:25][CH:24]=[N:23]4)=[CH:18][CH:17]=3)[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[C:5]2=[N:4]1

Participants

10

Reactant 6

HCID 887Methanol2×HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 4148881Lithium borohydride2×HCID 131732097HCID 131732097, compound

Product 1

HCID 68154041HCID 68154041, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Methyl [2-(3-oxo-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-3,5-dihydro-2H-pyrazolo[4,3-c]quinolin-2-yl)phenyl]acetate (Example 533, 0.10 g, 0.21 mmol) was suspended in diethyl ether (6 mL) and dichloromethane (9 mL), cooled to 0° C. and treated with lithium borohydride (4.9 mg, 0.23 mmol, 1.1 equiv) and then methanol (9.2 μL, 0.23 mmol, 1.1 equiv). The mixture was stirred at 0° C. for 15 minutes and then warmed to ambient temperature. After 20 minutes, the mixture was treated with additional lithium borohydride (10 mg, 0.46 mmol, 2.2 equiv) and methanol (20 μL, 0.46 mmol, 2.2 equiv) and stirred for an additional 1 hour at ambient temperature. The mixture was treated with ammonium chloride (3 mL, aqueous saturated) and stirred at ambient temperature for 15 minutes. The mixture was poured into water (20 mL) and extracted with dichloromethane (3×50 mL). The combined organic extracts were treated with dichloro-5,6-dicyanobenzoquinone (DDQ, 52 mg, 0.46 mmol, 2.2 equiv) and stirred for 45 minutes at ambient temperature. The mixture was treated with sodium bicarbonate (50 mL, aqueous saturated) and vigorously stirred for 30 minutes, partitioned and the aqueous layer was further extracted with dichloromethane (1×50 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate containing 5% methanol), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 9.13 (1H, s), 8.46 (1H, d, J=2.5 Hz), 8.19 (1H, d, J=7.6 Hz), 7.84 (2H, d, J=8.5 Hz), 7.77 (1H, d, J=8.5 Hz), 7.73 (1H, d, J=1.4 Hz), 7.64-7.59 (1H, m), 7.53 (1H, t, J=7.2 Hz), 7.48 (2H, d, J=8.5 Hz), 7.43 (1H, br d, J=6.9 Hz), 7.39-7.33 (3H, m), 6.53 (1H, m), 5.77 (2H, s), 4.61 (1H, t, J=5.2 Hz), 3.58-3.53 (2H, m), 2.77 (2H, t, J=7.4 Hz) ppm; high resolution mass spectrometry (ES+) m/z 462.1912 [(M+H)+; calculated for C28H24N5O2: 462.1925].

Workup

  1. temperaturewarmed to ambient temperature
  2. waitAfter 20 minutes
  3. stirringstirred for an additional 1 hour at ambient temperature
  4. stirringstirred at ambient temperature for 15 minutes
  5. extractionextracted with dichloromethane (3×50 mL)
  6. stirringstirred for 45 minutes at ambient temperature
  7. stirringvigorously stirred for 30 minutes
  8. custompartitioned
  9. extractionthe aqueous layer was further extracted with dichloromethane (1×50 mL)
  10. dry with materialThe combined organic extracts were dried with sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate containing 5% methanol)

Sources & evidence

ORD record
ord-5712dd3d5a6d47e0924dabf51a429e25
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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