Potassium Hydroxide → HCID 86647578, compound

HRID 2098582Notes

Reaction equation

HRID 2098582 reaction equation
Cl.[NH2:2][OH:3].[OH-].[K+].[CH:6]1([NH:9][C:10](=[O:42])/[C:11](/[C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=2)=[CH:12]/[C:13]2[CH:34]=[CH:33][C:16]([C:17]([NH:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([CH:27]=[CH:28][C:29](OC)=[O:30])=[CH:23][CH:22]=3)=[O:18])=[CH:15][CH:14]=2)[CH2:8][CH2:7]1>CO.C(Cl)Cl.O>[CH:6]1([NH:9][C:10](=[O:42])[C:11]([C:35]2[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=2)=[CH:12][C:13]2[CH:34]=[CH:33][C:16]([C:17]([NH:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24](/[CH:27]=[CH:28]/[C:29]([NH:2][OH:3])=[O:30])=[CH:23][CH:22]=3)=[O:18])=[CH:15][CH:14]=2)[CH2:7][CH2:8]1

Participants

7

Reactant 3

HCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 68768186HCID 68768186, compound

Product 1

HCID 86647578HCID 86647578, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Hydroxylamine hydrochloride (0.5 g, 7.2 mmol) in methanol (2 mL) was mixed with KOH (0.4 g, 7.2 mmol) in methanol (2 mL) at 0° C., and sonicated for 2 minutes and the white precipitate formed was filtered. The filtrate was added to methyl 3(4-((4-(1E)-(3-(cyclopropylamino)-2-(4-fluorophenyl)-3-oxoprop-1-enyl)benzamido)methyl)phenyl)acrylate (0.20 g, 0.4 mmol) in DCM (1.5 mL) and the mixture stirred at room temperature for 30 minutes. The reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (3×100 mL). The ethyl acetate layers were washed with water (100 mL), dried over anhydrous Na2SO4 and concentrated to obtain a crude compound, which was triturated with DCM (15 mL) to obtain a solid which was filtered and washed with DCM (5 mL) to afford the title compound (0.050 g, 25% yield). 1H NMR (DMSO-d6) δ (ppm): 0.51-052 (2H, m, —CH2), 0.63-0.65 (2H, m, —CH2), 2.74-2.75 (1H, m, —CH), 4.43-4.44 (2H, d, CH2), 6.39-6.43 (1H, d, ═CH), 7.05-7.07 (2H, d, Ar—H), 7.16-7.22 (4H, m, Ar—H), 7.29-7.32 (3H, m, Ar—H and ═CH), 7.40-7.44 (1H, d, ═CH), 7.49-7.51 (2H, d, Ar—H), 7.68-7.70 (2H, d, Ar—H), 7.89-7.90 (1H, d, —NH), 9.00 (2H, m, NH and OH), 10.73 (1H, s, NH), MS m/z: 498.1 (M+−1).

Workup

  1. customsonicated for 2 minutes
  2. customthe white precipitate formed
  3. filtrationwas filtered
  4. extractionextracted with ethyl acetate (3×100 mL)
  5. washThe ethyl acetate layers were washed with water (100 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customto obtain a crude compound, which
  9. customwas triturated with DCM (15 mL)
  10. customto obtain a solid which
  11. filtrationwas filtered
  12. washwashed with DCM (5 mL)

Sources & evidence

ORD record
ord-2e18b7ec93e34d05ba340d5898343c43
Source dataset
uspto-grants-2013_05
Patent number
US08450525B2

Reaction notes

Loading…