Diisopropylethylamine → Tert-butyl 4-((3-methyl-1,2,4-oxadiazol-5-yl)(6-(4-methylthiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)methyl)piperidine-1-carboxylate

HRID 335156Notes

Reaction equation

HRID 335156 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([S:18][C:19]2[CH:20]=[N:21][C:22]([NH:32][C:33]3[S:34][CH:35]=[C:36]([CH3:38])[N:37]=3)=[C:23]([O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:24]=2)[C:15](O)=[O:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)C(C)C)C.CN(C(F)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O[NH:64][C:65](=[NH:67])[CH3:66]>CN(C=O)C.CCOC(C)=O>[CH3:66][C:65]1[N:67]=[C:15]([CH:14]([S:18][C:19]2[CH:20]=[N:21][C:22]([NH:32][C:33]3[S:34][CH:35]=[C:36]([CH3:38])[N:37]=3)=[C:23]([O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:24]=2)[CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:13][CH2:12]2)[O:16][N:64]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 866315022-(1-(Tert-butoxycarbonyl)piperidin-4-yl)-2-(6-(4-methylthiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)acetic acidHCID 178465666HCID 178465666, compound

Product 1

HCID 86659295Tert-butyl 4-((3-methyl-1,2,4-oxadiazol-5-yl)(6-(4-methylthiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)methyl)piperidine-1-carboxylateYield 45.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Placed 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-(6-(4-methylthiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)acetic acid (0.250 g, 0.449 mmol), N-ethyl-N-isopropylpropan-2-amine (0.0638 g, 0.494 mmol) in DMF (10 mL) and added N-((dimethylamino)fluoromethylene)-N-methylmethanaminium hexafluorophosphate(V) (0.119 g, 0.449 mmol) and stirred for 30 minutes. Added N-hydroxyacetamidine (0.0366 g, 0.494 mmol) and heated to 110° C. for 4 days. The reaction was diluted with EtOAc and washed with water, dried, filtered and concentrated. The residue was purified by reverse phase chromatography to provide the title compound (0.122 g, 35.6%) Product was contaminated with ˜15% acid. Crude material was used in Step B.

Workup

  1. washwashed with water
  2. customdried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-3ba9cf79ff7447519657eedb789b9ef0
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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