Diisopropylethylamine → 3-[(1S)-2-Hydroxy-1-methylethoxy]-5-{4-[(2-methylazetidin-1-yl)carbonyl]phenoxy}-N-(5-methylpyrazin-2-yl)benzamide

HRID 20573Notes

Reaction equation

HRID 20573 reaction equation
CC[N:3]([CH:7]([CH3:9])[CH3:8])[CH:4](C)C.[OH:10][CH2:11][C@H:12]([CH3:40])[O:13][C:14]1[CH:15]=[C:16]([CH:27]=[C:28]([C:30]([NH:32][C:33]2[CH:38]=[N:37][C:36]([CH3:39])=[CH:35][N:34]=2)=[O:31])[CH:29]=1)[O:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC1CCN1>CN(C=O)C.C(OCC)(=O)C>[OH:10][CH2:11][C@H:12]([CH3:40])[O:13][C:14]1[CH:29]=[C:28]([CH:27]=[C:16]([O:17][C:18]2[CH:26]=[CH:25][C:21]([C:22]([N:3]3[CH2:4][CH2:9][CH:7]3[CH3:8])=[O:24])=[CH:20][CH:19]=2)[CH:15]=1)[C:30]([NH:32][C:33]1[CH:38]=[N:37][C:36]([CH3:39])=[CH:35][N:34]=1)=[O:31]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5334602-MethylazetidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 593469134-(3-[(1S)-2-hydroxy-1-methylethoxy]-5-{[(5-methylpyrazin-2-yl)amino]carbonyl}phenoxy)benzoic acid

Product 1

HCID 116914263-[(1S)-2-Hydroxy-1-methylethoxy]-5-{4-[(2-methylazetidin-1-yl)carbonyl]phenoxy}-N-(5-methylpyrazin-2-yl)benzamideYield 43.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIPEA (0.20 mL, 1.04 mmol) was added to a suspension of 4-(3-[(1S)-2-hydroxy-1-methylethoxy]-5-{[(5-methylpyrazin-2-yl)amino]carbonyl}phenoxy)benzoic acid (0.11 g, 0.26 mmol), HATU (210 mg, 0.55 mmol) and 2-methylazetidine (37 mg, 0.52 mmol) in DMF (3 mL) and the mixture stirred at ambient temperature for 24 hours. Ethyl acetate (30 mL) was added and washed with water (3×20 mL), brine (20 mL), dried (MgSO4), filtered and evaporated to a residue which was chromatographed on silica, eluting with a gradient of 0-20% methanol in ethyl acetate, to give the desired compound (54 mg).

Workup

  1. washwashed with water (3×20 mL), brine (20 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customevaporated to a residue which
  5. customwas chromatographed on silica
  6. washeluting with a gradient of 0-20% methanol in ethyl acetate

Sources & evidence

ORD record
ord-7c74d6756e6c4ddf8387248a2cb69d51
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

Loading…