Diisopropylethylamine → 5-(1,3-oxazol-2-yl)-N3,N3-dipropylisophthalamide

HRID 14281Notes

Reaction equation

HRID 14281 reaction equation
[CH2:1]([N:4]([CH2:21][CH2:22][CH3:23])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([C:16]2[O:17][CH:18]=[CH:19][N:20]=2)[CH:15]=1)[C:10](O)=[O:11])=[O:6])[CH2:2][CH3:3].C([N:27](CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[O:17]1[CH:18]=[CH:19][N:20]=[C:16]1[C:14]1[CH:15]=[C:7]([C:5]([N:4]([CH2:21][CH2:22][CH3:23])[CH2:1][CH2:2][CH3:3])=[O:6])[CH:8]=[C:9]([CH:13]=1)[C:10]([NH2:27])=[O:11]

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210628933-(Dipropylcarbamoyl)-5-(oxazol-2-yl)benzoic acid

Product 1

HCID 575125725-(1,3-oxazol-2-yl)-N3,N3-dipropylisophthalamideYield 148.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoic acid 38 (120 mg, 0.38 mmol) in methylene chloride (3.8 mL) containing N,N-diisopropylethylamine (132 μL, 0.76 mmol) and HBTU (151 mg, 0.40 mmol) was stirred at room temperature for 0.5 h. To the above solution was added a solution of the orange oil from step 7 (207 mg, 0.57 mmol) in methylene chloride (3.8 mL) containing N,N-diisopropylethylamine (132 μL, 0.76 mmol) and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was then diluted with additional methylene chloride and washed with saturated sodium bicarbonate and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to yield an oily residue. Purification by flash column chromatography (silica, 90:10 methylene chloride/methanol) gave N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[({2-(dimethylamino)methyl]pyridin-4-yl}methyl)amino]-2-hydroxypropyl}-5-(1,3-oxazol-2-yl)-N3,N3-dipropylisophthalamide (178 mg): mp 63-66° C.; ESI MS m/z 663 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 18 h
  2. washwashed with saturated sodium bicarbonate and saturated sodium chloride
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto yield an oily residue
  7. customPurification by flash column chromatography (silica, 90:10 methylene chloride/methanol)

Sources & evidence

ORD record
ord-31ead9ae788a46dca55fd4931a7677e0
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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