Ammonium Chloride → 2-(4-(2-(Trifluoromethyl)phenoxy)piperidin-1-yl)thiazole-5-carboxamide

HRID 561200Notes

Reaction equation

HRID 561200 reaction equation
[F:1][C:2]([F:25])([F:24])[C:3]1[CH:23]=[CH:22][CH:21]=[CH:20][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[S:13][C:14]([C:17](O)=[O:18])=[CH:15][N:16]=2)[CH2:8][CH2:7]1.C1C=CC2N(O)N=[N:32]C=2C=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH4+].[Cl-].CCN(C(C)C)C(C)C>CN(C=O)C>[F:25][C:2]([F:1])([F:24])[C:3]1[CH:23]=[CH:22][CH:21]=[CH:20][C:4]=1[O:5][CH:6]1[CH2:7][CH2:8][N:9]([C:12]2[S:13][C:14]([C:17]([NH2:32])=[O:18])=[CH:15][N:16]=2)[CH2:10][CH2:11]1

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666968024-[2-(Trifluoromethyl)phenoxy]piperidin-1-yl-1,3-thiazole-5-carboxylic acid

Product 1

HCID 468806672-(4-(2-(Trifluoromethyl)phenoxy)piperidin-1-yl)thiazole-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3-thiazole-5-carboxylic acid (14.5 g, 39 mmol), HOBt (5.3 g, 39 mmol)), HATU (23.7 g, 62 mmol) and NH4Cl (6.3 g, 117 mmol) in DMF (200 mL) at room temperature was added Hünig's base (34 mL, 195 mmol) over about 15 min. The mixture was stirred at room temperature overnight. After dilution with water, the mixture was extracted twice with EtOAc. The EtOAc extracts were combined, washed with 0.5 N NaOH (2×), diluted brine (1×), dried (Na2SO4) and concentrated. The residue was triturated with Et2O/hexanes (1:1) to give the title compound as a pale yellow solid. 1H NMR (500 MHz, acetone-d6): δ7.79 (s, 1H), 7.67-7.61 (m, 2H), 7.38 (d, 1H), 7.12 (t, 1H), 5.02 (s, 1H), 3.76 (t, 2H), 3.71-3.67 (m, 2H), 2.16 (t, 2H), 2.00-1.94 (m, 2H).

Workup

  1. extractionAfter dilution with water, the mixture was extracted twice with EtOAc
  2. washwashed with 0.5 N NaOH (2×), diluted brine (1×)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was triturated with Et2O/hexanes (1:1)

Sources & evidence

ORD record
ord-4be4b7674a2e4ecebaf94970fa96e13c
Source dataset
uspto-grants-2011_11
Patent number
US08063224B2

Reaction notes

Loading…