Diisopropylethylamine → ((2S,3R)-2-(Hydroxymethyl)-3-methylpiperidin-1-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone

HRID 61029Notes

Reaction equation

HRID 61029 reaction equation
[CH3:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][NH:4][C@@H:3]1[CH2:8][OH:9].CCN(C(C)C)C(C)C.[CH3:19][C:20]1[CH:21]=[CH:22][C:23]([N:29]2[N:33]=[CH:32][CH:31]=[N:30]2)=[C:24]([CH:28]=1)[C:25](O)=[O:26].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC(N(C)C)=O>[OH:9][CH2:8][C@@H:3]1[C@H:2]([CH3:1])[CH2:7][CH2:6][CH2:5][N:4]1[C:25]([C:24]1[CH:28]=[C:20]([CH3:19])[CH:21]=[CH:22][C:23]=1[N:29]1[N:33]=[CH:32][CH:31]=[N:30]1)=[O:26]

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 21825032((2S,3R)-3-Methylpiperidin-2-yl)methanolHCID 532601655-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid

Product 1

HCID 117727618((2S,3R)-2-(Hydroxymethyl)-3-methylpiperidin-1-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

((2S,3R)-3-Methylpiperidin-2-yl)methanol from the previous step in DMA (0.2M) was added DIPEA (2 equiv.) followed by 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid (1.2 eq) and HATU (1.1 equiv.). The reaction was allowed to stir at rt for 15 h, and was then concentrated in vacuo to remove the DMAC. The crude residue was taken up in EtOAc and washed with 1M HCl, sat aq. NaHCO3, brine, dried (MgSO4), and concentrated. The crude residue was purified by chromatography on silica gel (EtOAc/hexanes) to give the title compound as a brown oil which crystallized (2.6 g). MS (ESI) 315 (M+H).

Workup

  1. concentrationwas then concentrated in vacuo
  2. customto remove the DMAC
  3. washwashed with 1M HCl
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe crude residue was purified by chromatography on silica gel (EtOAc/hexanes)

Sources & evidence

ORD record
ord-afb1ba5122ec4541b41b3d9a8a4ac77b
Source dataset
uspto-grants-2016_09
Patent number
US09440982B2

Reaction notes

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