Diisopropylethylamine → Rac-trans-tert-butyl ((1-(5-(4-fluorophenyl)-2-methylthiazole-4-carbonyl)-3-methylpiperidin-2-yl)methyl)carbamate

HRID 60854Notes

Reaction equation

HRID 60854 reaction equation
[CH3:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][NH:4][C@H:3]1[CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13].CCN(C(C)C)C(C)C.[F:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[S:37][C:36]([CH3:38])=[N:35][C:34]=2[C:39](O)=[O:40])=[CH:29][CH:28]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:26][C:27]1[CH:28]=[CH:29][C:30]([C:33]2[S:37][C:36]([CH3:38])=[N:35][C:34]=2[C:39]([N:4]2[CH2:5][CH2:6][CH2:7][C@@H:2]([CH3:1])[C@@H:3]2[CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:40])=[CH:31][CH:32]=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 223241255-(4-Fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acidHCID 95378399trans-N-Boc-1-(3-methylpiperidin-2-YL)methanamine

Product 1

HCID 131737141Rac-trans-tert-butyl ((1-(5-(4-fluorophenyl)-2-methylthiazole-4-carbonyl)-3-methylpiperidin-2-yl)methyl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of rac-trans-tert-butyl ((3-methylpiperidin-2-yl)methyl)carbamate (1 eq) from the previous step in DMF was added DIPEA (2 eq) followed by 5-(4-fluorophenyl)-2-methylthiazole-4-carboxylic acid (1.5 eq) and HATU (2 eq). The reaction was allowed to stir at rt for 15 h, and was then concentrated in vacuo to remove the DMF. 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/hex) to give tert-butyl (((2R,3R)-1-(5-(4-fluorophenyl)-2-methylthiazole-4-carbonyl)-3-methylpiperidin-2-yl)methyl)carbamate as a light yellow oil. To a solution of this carbamate in CH2Cl2 was added TFA (1:1 v/v). The reaction was aged at rt and monitored for disappearance of starting material by analytical reverse-phase HPLC. When starting material was consumed, the reaction was concentrated in vacuo. The crude residue was taken up in EtOAc, and washed with sat aqueous NaHCO3, brine, dried (MgSO4), and concentrated to afford the title compound as a pale yellow oil which crystallized. MS (ESI) 348.2 (M+H).

Workup

  1. concentrationwas then concentrated in vacuo
  2. customto remove the DMF
  3. washwashed with 1M 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-c82bac2407bc47a581311720685982ae
Source dataset
uspto-grants-2016_09
Patent number
US09440982B2

Reaction notes

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