Hydrochloric Acid → 5-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde oxime

HRID 1256250Notes

Reaction equation

HRID 1256250 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([CH:19]=O)[CH:15]=[CH:14][C:13]=2[C:12]2[NH:21][N:22]=[C:23]([NH:24][CH:25]3[CH2:30][CH2:29][N:28]([S:31]([CH2:34][CH3:35])(=[O:33])=[O:32])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1.[NH2:36][OH:37].Cl>N1C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([CH:19]=[N:36][OH:37])[CH:15]=[CH:14][C:13]=2[C:12]2[NH:21][N:22]=[C:23]([NH:24][CH:25]3[CH2:30][CH2:29][N:28]([S:31]([CH2:34][CH3:35])(=[O:33])=[O:32])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 497643955-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde

Product 1

HCID 1363367475-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde oximeYield 71.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A 25 ml round-bottomed flask is charged with 30 mg of 5-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde, prepared in example 19, in 2 ml of pyridine. 7 mg of hydroxylamine as the hydrochloride are added. After 1 h at RT, the mixture is evaporated under RP. The product is purified by flash chromatography on silica gel (15-40 μm), eluting with a DCM/methanol mixture (95/5 by vol.), to give 22 mg of 5-(2,6-difluorophenyl)-3-{[1-(ethylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde oxime (yellow solid). 1H NMR (500 MHz, DMSO-d6) δ ppm with the E or Z isomerism: 1.23 (t, J=7.4 Hz, 3 H) 1.63 (m, 2 H) 2.09 (m, 2 H) 2.97 (m, 2 H) 3.05 (q, J=7.4 Hz, 2 H) 3.61 (m, 2 H) 3.80 (m, 1 H) 6.08 (broad m, 1 H) 7.33 (m, 2 H) 7.66 (m, 1 H) 7.86 (broad s, 1 H) 8.14 (broad d, J=8.3 Hz, 1 H) 8.30 (5, 1 H) 8.41 (d, J=8.3 Hz, 1 H) 11.45 (broad m, 1 H) 12.82 (broad m, 1 H). [M+H]+m/z=515.

Workup

  1. customthe mixture is evaporated under RP
  2. customThe product is purified by flash chromatography on silica gel (15-40 μm)
  3. washeluting with a DCM/methanol mixture (95/5 by vol.)

Sources & evidence

ORD record
ord-a06b783679914962920371300bc00af0
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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