Diisopropylethylamine → {3-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)-5-[4-(difluoromethoxy)phenyl]piperidin-1-yl}(1,1-dioxidothiomorpholin-4-yl)methanone

HRID 220060Notes

Reaction equation

HRID 220060 reaction equation
[F:1][CH:2]([F:29])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][N:14]([C:16]([N:18]3[CH2:23][CH2:22][S:21](=[O:25])(=[O:24])[CH2:20][CH2:19]3)=[O:17])[CH2:13][CH:12]([C:26]([OH:28])=O)[CH2:11]2)=[CH:6][CH:5]=1.O[NH:31][C:32]([CH:34]1[CH2:36][CH2:35]1)=[NH:33].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH:34]1([C:32]2[N:33]=[C:26]([CH:12]3[CH2:11][CH:10]([C:7]4[CH:6]=[CH:5][C:4]([O:3][CH:2]([F:29])[F:1])=[CH:9][CH:8]=4)[CH2:15][N:14]([C:16]([N:18]4[CH2:23][CH2:22][S:21](=[O:25])(=[O:24])[CH2:20][CH2:19]4)=[O:17])[CH2:13]3)[O:28][N:31]=2)[CH2:36][CH2:35]1

Participants

6

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 581165675-[4-(Difluoromethoxy)phenyl]-1-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]piperidine-3-carboxylic acidHCID 178513214HCID 178513214, compound

Product 1

HCID 59606595{3-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)-5-[4-(difluoromethoxy)phenyl]piperidin-1-yl}(1,1-dioxidothiomorpholin-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

100 mg (0.23 mmol) of the compound from Example 37A and 46 mg (0.46 mmol) of N-hydroxycyclopropanecarboximidamide were initially charged in 0.8 ml of DMF and reacted with 132 mg (0.35 mmol) of HATU and 0.12 ml (90 mg, 0.69 mmol) of N,N-diisopropylethylamine. The reaction mixture was stirred at RT for 15 minutes and then partitioned between water and ethyl acetate. The organic phase was washed repeatedly with water, dried over sodium sulphate and concentrated under reduced pressure. The residue was taken up in 3.0 ml of DMF and converted in a microwave at 180° C. for 2 minutes. The reaction mixture was purified by means of preparative HPLC. Yield: 46 mg (37% of theory)

Workup

  1. custompartitioned between water and ethyl acetate
  2. washThe organic phase was washed repeatedly with water
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. waitconverted in a microwave at 180° C. for 2 minutes
  6. customThe reaction mixture was purified by means of preparative HPLC

Sources & evidence

ORD record
ord-b69f17abf5104e7c9c956b50d60244e7
Source dataset
uspto-grants-2012_06
Patent number
US08202862B2

Reaction notes

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