Hydrochloric Acid → HCID 57812427, compound

HRID 912006Notes

Reaction equation

HRID 912006 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([C:11]3[CH:12]=[C:13]([CH:16]=O)[S:14][CH:15]=3)=[CH:9][O:10][C:4]=2[C:3]=1[O:18][C@@H:19]([C:21]1[C:26]([Cl:27])=[CH:25][CH:24]=[C:23]([F:28])[C:22]=1[Cl:29])[CH3:20].Cl.[NH2:31]O.C([O-])(=O)C.[K+].C(O)C.Cl.C1COCC1>O.[Zn]>[NH2:31][CH2:16][C:13]1[S:14][CH:15]=[C:11]([C:8]2[C:5]3[CH:6]=[N:7][C:2]([NH2:1])=[C:3]([O:18][C@@H:19]([C:21]4[C:26]([Cl:27])=[CH:25][CH:24]=[C:23]([F:28])[C:22]=4[Cl:29])[CH3:20])[C:4]=3[O:10][CH:9]=2)[CH:12]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 702EthanolHCID 8028TetrahydrofuranHCID 443297Hydroxyamine hydrochlorideHCID 517044Potassium AcetateHCID 57812598HCID 57812598, compound

Product 1

HCID 57812427HCID 57812427, compound

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 962WaterSolvent

Procedure

A mixture of 4-{6-amino-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-3-yl}thiophene-2-carbaldehyde (10.0 mg, 0.0222 mmol), hydroxylamine hydrochloride (1.85 mg, 0.0266 mmol), potassium acetate, (2.61 mg, 0.0266 mmol) and ethanol (1.0 mL, 17 mmol) was stirred at room temperature for 20 minutes. The solution was concentrated in vacuo and extracted with DCM and sat. NaHCO3. The organic layer was concentrated in vacuo. Zinc (14.5 mg, 0.222 mmol), 2 M of HCl in H2O (0.5 mL) and THF (1.0 mL, 12 mmol) were added. The mixture was refluxed at 70° C. for 3 hours. The solution was concentrated in vacuo and extracted with DCM and sat. NaHCO3. The organic layer was concentrated in vacuo and dissolved in DMSO. The sample was purified by the MDPS to afford the title compound as white solid. MS (ES+): m/z 452.08/454.05 (100/75) [MH+]. HPLC: tR=0.62 min (HPLC-ACQUITY, Analytical). 1H NMR (400 MHz, CD3OD): δ=1.91 (d, J=6.6 Hz, 3H), 4.33 (s, 2H), 6.55 (q, J=6.8 Hz, 1H), 7.23 (t, J=8.6 Hz, 1H), 7.41 (dd, J=9.0, 4.9 Hz, 1H), 7.51 (s, 1H), 7.77 (d, J=1.3 Hz, 1H), 7.89 (s, 1H), 8.24 (s, 1H).

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. extractionextracted with DCM and sat. NaHCO3
  3. concentrationThe organic layer was concentrated in vacuo
  4. temperatureThe mixture was refluxed at 70° C. for 3 hours
  5. concentrationThe solution was concentrated in vacuo
  6. extractionextracted with DCM and sat. NaHCO3
  7. concentrationThe organic layer was concentrated in vacuo
  8. dissolutiondissolved in DMSO
  9. customThe sample was purified by the MDPS

Sources & evidence

ORD record
ord-eebf20ea38904216867feead54675335
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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