Methanol → HCID 86647577, compound

HRID 2098573Notes

Reaction equation

HRID 2098573 reaction equation
Cl.[NH2:2][OH:3].[OH-:4].[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:18]=[CH:17][C:16]([CH:19]=[CH:20][C:21]([NH:23][CH2:24][C:25]3[CH:26]=[C:27]([CH:32]=[CH:33][CH:34]=3)C(OC)=O)=[O:22])=[CH:15][CH:14]=2)[CH2:8][CH2:7]1.[CH3:43]O>C(Cl)Cl.O>[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:14]=[CH:15][C:16]([CH:19]=[CH:20][C:21]([NH:23][CH2:24][C:25]3[CH:26]=[CH:27][C:32]([C:43]([NH:2][OH:3])=[O:4])=[CH:33][CH:34]=3)=[O:22])=[CH:17][CH:18]=2)[CH2:7][CH2:8]1

Participants

7

Reactant 4

HCID 887Methanol2×HCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 68769911HCID 68769911, compound

Product 1

HCID 86647577HCID 86647577, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

Hydroxylamine hydrochloride (0.55 g, 8 mmol) in methanol (2 mL) was mixed with KOH (0.45 g, 8 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-((3-(4-(3-(cyclopropylamino)-2-(4-fluorophenyl)-3-oxoprop-1-enyl)phenyl)acrylamido)methyl)benzoate (0.22 g, 0.44 mmol) in DCM (1.5 mL) and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (1×200 mL). The ethyl acetate layer was washed with water (100 mL), dried over anhydrous Na2SO4 and concentrated to obtain a crude compound followed by trituration with DCM (15 mL). The obtained solid was filtered and washed with DCM (5 mL) to afford the title compound (0.044 g, 20% yield). 1H NMR (DMSO-d6) δ (ppm): 0.51 (2H, m, —CH2), 0.62-0.65 (2H, m, —CH2), 2.73-2.75 (1H, m, —CH), 4.37-4.38 (2H, d, —CH2), 6.62-6.66 (1H, d, ═CH), 7.00-7.02 (2H, d, Ar—H), 7.15-7.19 (3H, m, Ar—H), 7.21-7.27 (3H, d, Ar—H and ═CH), 7.35 (2H, d, Ar—H), 7.38-7.40 (2H, m, Ar—H and NH), 7.69-7.71 (2H, d, Ar—H), 7.83-7.84 (1H, d, ═CH), 8.63 (1H, t, NH). MS m/z: 500.1 (M++1).

Workup

  1. customsonicated for 2 minutes
  2. customthe white precipitate formed
  3. filtrationwas filtered
  4. extractionextracted with ethyl acetate (1×200 mL)
  5. washThe ethyl acetate layer was washed with water (100 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customto obtain a crude compound
  9. filtrationThe obtained solid was filtered
  10. washwashed with DCM (5 mL)

Sources & evidence

ORD record
ord-e193e31fdb364a5d82f01ddb8de304b1
Source dataset
uspto-grants-2013_05
Patent number
US08450525B2

Reaction notes

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