Hydrochloric Acid → HCID 178504949, compound

HRID 1256245Notes

Reaction equation

HRID 1256245 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]([C:19]#[N:20])[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]([CH3:34])(=[O:33])=[O:32])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1.CO.[NH2:37][OH:38].Cl>O.C(N(CC)CC)C.C1COCC1>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([C:19](=[NH:20])[NH:37][OH:38])[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]([CH3:34])(=[O:32])=[O:33])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 887MethanolHCID 49764269HCID 49764269, compound

Product 1

HCID 178504949HCID 178504949, compoundYield 30.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
65 °C

Procedure

A 10 ml round-bottomed flask is charged with 30 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile, prepared in example 12, 1.3 ml of methanol, 0.8 ml of THF and 62 mg of triethylamine. 44 mg of hydroxylamine as the hydrochloride are added. The mixture is heated at 65° C. for 3 h and then evaporated under RP. The solid obtained is taken up in 10 ml of water and extracted with AcOEt. The organic phase is dried over MgSO4, filtered and concentrated under RP. It is purified by flash chromatography on silica gel (15-40 μm), eluting with DCM and then with a DCM/methanol mixture (80/20 by vol.), to give 9.7 mg of 5-(2,6-difluorophenyl)-N-hydroxy-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carboximidamide in the form of a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.67 (m, 2 H) 2.11 (m, 2 H) 2.91 (m, 2 H) 2.87 (s, 3 H) 3.56 (m, 2 H) 3.79 (m, 1 H) 5.95 (broad s, 2 H) 6.03 (d, J=7.9 Hz, 1 H) 7.31 (m, 2 H) 7.66 (m, 1 H) 7.95 (broad s, 1 H) 8.18 (dd, J=8.5, 1,6 Hz, 1H) 8.39 (d, J=8.5 Hz, 1 H) 9.82 (s, 1 H) 12.76 (s, 1H). LC-MS-DAD-ELSD: 516 (+)=(M+H)(+).

Workup

  1. customevaporated under RP
  2. customThe solid obtained
  3. extractionextracted with AcOEt
  4. dry with materialThe organic phase is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under RP
  7. customIt is purified by flash chromatography on silica gel (15-40 μm)
  8. washeluting with DCM

Sources & evidence

ORD record
ord-c22f911f9c76450193321859ecab7701
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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