Diisopropylethylamine → N-(3-Hydroxy-4-(methoxyamino)-4-oxo-1-phenylbutan-2-yl)-2-(2-phenylthiazol-4-yl)nicotinamide

HRID 1400235Notes

Reaction equation

HRID 1400235 reaction equation
CCN(C(C)C)C(C)C.[OH:10][CH:11]([CH:15]([NH:23][C:24](=[O:42])[C:25]1[CH:30]=[CH:29][CH:28]=[N:27][C:26]=1[C:31]1[N:32]=[C:33]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[S:34][CH:35]=1)[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:12](O)=[O:13].Cl.[CH3:44][O:45][NH2:46].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>ClCCl>[OH:10][CH:11]([C:12]([NH:46][O:45][CH3:44])=[O:13])[CH:15]([NH:23][C:24](=[O:42])[C:25]1[CH:30]=[CH:29][CH:28]=[N:27][C:26]=1[C:31]1[N:32]=[C:33]([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[S:34][CH:35]=1)[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 521874O-Methylhydroxylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 675402612-Hydroxy-4-phenyl-3-(2-(2-phenylthiazol-4-yl)nicotinamido)butanoic acid

Product 1

HCID 86644789N-(3-Hydroxy-4-(methoxyamino)-4-oxo-1-phenylbutan-2-yl)-2-(2-phenylthiazol-4-yl)nicotinamideYield 84.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

DIPEA (200 μl, 0.567 mmol) was added to a suspension of 2-hydroxy-4-phenyl-3-(2-(2-phenylthiazol-4-yl)nicotinamido)butanoic acid (250 mg, 0.544 mmol) and O-methylhydroxylamine hydrochloride (90 mg, 1.078 mmol) in dichloromethane (50 ml) at 5° C. After about 5 min 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate (HATU) (665 mg, 1.748 mmol) was added, the pH adjusted to 8 via addition of further DIPEA, and the mixture then stirred for 1 h at 5° C. and then overnight at room temperature. Then dichloromethane (50 ml) was added, washed 2× with 10 ml of water and brine, dried, filtered and concentrated to give 430 mg of the crude product which was purified by chromatography on silica gel (dichloromethane+11-12% methanol. Concentration of the combined fractions and drying afforded 224 mg of a white amorphous solid;

Workup

  1. customovernight
  2. customat room temperature
  3. washwashed 2× with 10 ml of water and brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give 430 mg of the crude product which
  8. customwas purified by chromatography on silica gel (dichloromethane+11-12% methanol
  9. customConcentration of the combined fractions and drying

Sources & evidence

ORD record
ord-4c038802be3f4d02ae974f08cef2710d
Source dataset
uspto-grants-2014_12
Patent number
US08906941B2

Reaction notes

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