Dimethylacetamide → rac-cis-(2-(Hydroxymethyl)-3-methylpiperidin-1-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone

HRID 60842Notes

Reaction equation

HRID 60842 reaction equation
[CH3:1]CN(C(C)C)C(C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[S:21][C:20]([CH3:22])=[N:19][C:18]=2[C:23]([OH:25])=O)=[CH:13][CH:12]=1.CN(C(ON1N=N[C:36]2[CH:37]=[CH:38][CH:39]=[N:40][C:35]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C[C:51](N(C)C)=[O:52]>>[OH:52][CH2:51][C@H:35]1[C@@H:36]([CH3:1])[CH2:37][CH2:38][CH2:39][N:40]1[C:23]([C:18]1[N:19]=[C:20]([CH3:22])[S:21][C:17]=1[C:14]1[CH:13]=[CH:12][C:11]([F:10])=[CH:16][CH:15]=1)=[O:25]

Participants

5

Reactant 4

HCID 31374DimethylacetamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 223241255-(4-Fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid

Product 1

HCID 131737133rac-cis-(2-(Hydroxymethyl)-3-methylpiperidin-1-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone

Procedure

To a solution of the product from the previous step (1.4 g) in DMAC was added DIPEA (2 eq) followed by 5-(4-fluorophenyl)-2-methylthiazole-4-carboxylic acid (2.3 g) and HATU (1.1 eq). 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 1 M HCl, sat aq. NaHCO3, brine, dried (MgSO4), and concentrated. The crude residue was purified by chromatography on silica gel (EtOAc/hex) to give the title compound as a brown oil which crystallized (2.6 g). MS (ESI) 349.4 (M+H).

Workup

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

Sources & evidence

ORD record
ord-c54c4013171e4db2a43a618c044aad5e
Source dataset
uspto-grants-2016_09
Patent number
US09440982B2

Reaction notes

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