Diisopropylethylamine → 4-benzyloxy-N-[3-tert-butyl-2-methoxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-2-fluoro-benzamide

HRID 2390875Notes

Reaction equation

HRID 2390875 reaction equation
[C:1]([C:5]1[C:6]([O:20][CH3:21])=[C:7]([NH2:19])[CH:8]=[C:9]([C:11]2[C:12]([O:17][CH3:18])=[N:13][CH:14]=[CH:15][CH:16]=2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:22]([O:29][C:30]1[CH:38]=[CH:37][C:33]([C:34](O)=[O:35])=[CH:32][C:31]=1F)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.[F:57][P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>O.CN(C=O)C>[CH2:22]([O:29][C:30]1[CH:38]=[CH:37][C:33]([C:34]([NH:19][C:7]2[CH:8]=[C:9]([C:11]3[C:12]([O:17][CH3:18])=[N:13][CH:14]=[CH:15][CH:16]=3)[CH:10]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[C:6]=2[O:20][CH3:21])=[O:35])=[C:32]([F:57])[CH:31]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 187575074-(Benzyloxy)-3-fluorobenzoic acidHCID 670698823-Tert-butyl-2-methoxy-5-(2-methoxypyridin-3-yl)phenylamine

Product 1

HCID 670699134-benzyloxy-N-[3-tert-butyl-2-methoxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-2-fluoro-benzamideYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

step 1—A solution of 100 (100 mg, 0.349 mmol, 4-benzyloxy-3-fluoro-benzoic acid (86 mg, 0.349 mmol), HATU (146 mg, 0.384 mmol, DIPEA (0.122 mL, 0.698 mmol), and DMF (3 mL) is stirred at 50° under Ar overnight. The reaction was cooled, diluted with H2O and extracted with EtOAc. The combined extracts were washed with H2O, dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 eluting with 20% EtOAc/hexane to afford 0.125 g (85%) of 4-benzyloxy-N-[3-tert-butyl-2-methoxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-2-fluoro-benzamide (322) which could be recrystallized from EtOAc.

Workup

  1. temperatureThe reaction was cooled
  2. extractionextracted with EtOAc
  3. washThe combined extracts were washed with H2O
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by SiO2 eluting with 20% EtOAc/hexane

Sources & evidence

ORD record
ord-320bc3aaa98b474dae8c6d199fa38c53
Source dataset
uspto-grants-2012_09
Patent number
US08273773B2

Reaction notes

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