Acetic Acid → HCID 52914257, compound

HRID 341037Notes

Reaction equation

HRID 341037 reaction equation
[F:1][C:2]1[C:11]2[N:10]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:15][CH:14]=3)[CH:9]=[C:8]3[C:24](=[O:35])[N:25]([C:27]4[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=4[CH:29]=O)[N:26]=[C:7]3[C:6]=2[C:5]([F:36])=[CH:4][CH:3]=1.[CH2:37]([NH2:39])[CH3:38].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>C(#N)C.ClCCl>[CH2:37]([NH:39][CH2:29][C:28]1[CH:31]=[CH:32][CH:33]=[CH:34][C:27]=1[N:25]1[C:24](=[O:35])[C:8]2=[CH:9][N:10]([CH2:12][C:13]3[CH:14]=[CH:15][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:17][CH:18]=3)[C:11]3[C:2]([F:1])=[CH:3][CH:4]=[C:5]([F:36])[C:6]=3[C:7]2=[N:26]1)[CH3:38]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 6341EthylamineHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 5049666Sodium triacetoxyborohydrideHCID 86668674HCID 86668674, compound

Product 1

HCID 52914257HCID 52914257, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

2-(6,9-Difluoro-3-oxo-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-3,5-dihydro-2H-pyrazolo[4,3-c]quinolin-2-yl)benzaldehyde [(Example 39) 15 mg, 0.031 mmol] was suspended in acetonitrile (1.5 mL), treated with ethylamine (0.15 mL, 0.15 mmol, 1.0 M tetrahydrofuran solution, 5 equiv), acetic acid (10 μL, 0.17 mmol, 5.6 equiv) and powdered 4 Å molecular sieves (15 mg, 1 wt equiv) and stirred for 30 minutes at ambient temperature. Sodium triacetoxyborohydride (6.6 mg, 0.031 mmol, 1 equiv) was added and the mixture was stirred for 3 hours at ambient temperature. The mixture was diluted with dichloromethane (5 mL), filtered and concentrated in vacuo. The residue was diluted with dimethylsulfoxide (1 mL) and water (0.1 mL) and treated with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ, 7.0 mg, 0.031 mmol, 1 equiv). After stirring for 30 minutes, the mixture was filtered and purified by preparative reverse phase HPLC (5:95 to 95:5; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid:acetonitrile), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 9.24 (1H, s), 8.80 (2H, br s), 8.47 (1H, d, J=2.5 Hz), 7.82 (2H, d, J=8.7 Hz), 7.73-7.68 (3H, m), 7.64-7.58 (2H, m), 7.55-7.50 (2H, m), 7.35 (2H, d, J=8.6 Hz), 6.54 (1H, dd, J=2.4, 1.9 Hz), 5.86 (2H, d, J=3.2 Hz), 4.16 (2H, br m), 2.97-2.92 (2H, m), 0.91 (3H, t, J=7.5 Hz) ppm; high resolution mass spectrometry (ES+) m/z 511.2035 [(M+H)+; calculated for C29H25F2N6O: 511.2053].

Workup

  1. stirringthe mixture was stirred for 3 hours at ambient temperature
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. additionThe residue was diluted with dimethylsulfoxide (1 mL) and water (0.1 mL)
  5. stirringAfter stirring for 30 minutes
  6. filtrationthe mixture was filtered
  7. custompurified by preparative reverse phase HPLC (5:95 to 95:5; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid:acetonitrile)

Sources & evidence

ORD record
ord-0fdd0e75982745b4bedea5d43d42798d
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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