Diisopropylethylamine → HCID 66850147, compound

HRID 1846964Notes

Reaction equation

HRID 1846964 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[N:7]2[CH:8]=[C:9]([C:12]3[CH:20]=[CH:19][C:15]([C:16](O)=[O:17])=[CH:14][CH:13]=3)[CH:10]=[CH:11][C:6]2=[N:5][N:4]=1.Cl.[F:24][C:25]1([F:29])[CH2:28][NH:27][CH2:26]1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:24][C:25]1([F:29])[CH2:28][N:27]([C:16]([C:15]2[CH:19]=[CH:20][C:12]([C:9]3[CH:10]=[CH:11][C:6]4[N:7]([C:3]([C:2]([F:1])([F:21])[F:22])=[N:4][N:5]=4)[CH:8]=3)=[CH:13][CH:14]=2)=[O:17])[CH2:26]1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 27582473,3-Difluoroazetidine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 58119001HCID 58119001, compound

Product 1

HCID 66850147HCID 66850147, compoundYield 57.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)benzoic acid (52 mg) was dissolved in DMF (2 mL). 3,3-difluoroazetidine hydrochloride (26 mg), diisopropylethylamine (35 μL) and HATU (93 mg) were added sequentially. After 24 h, added additional amounts of Diisopropylethylamine (105 μL) and HATU (279 mg). When the reaction was mostly complete, quenched with ethyl acetate/water, washed with 0.1N HCl, and concentrated NaHCO3. Purified on prep-TLC plate using 5% MeOH/dichloromethane. Isolated 37 mg of (3,3-difluoroazetidin-1-yl)(4-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)phenyl)methanone (57%).

Workup

  1. customquenched with ethyl acetate/water
  2. washwashed with 0.1N HCl, and concentrated NaHCO3
  3. customPurified on prep-TLC plate

Sources & evidence

ORD record
ord-99fdbfc3aeac495489dc73139fe231fc
Source dataset
uspto-grants-2015_02
Patent number
US08952034B2

Reaction notes

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