Ammonium Chloride → 2-{3-[2-(Trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carboxamide

HRID 2355060Notes

Reaction equation

HRID 2355060 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:22]=[CH:21][CH:20]=[CH:19][C:4]=1[O:5][CH:6]1[CH2:10][CH2:9][N:8]([C:11]2[S:12][C:13]([C:16]([OH:18])=O)=[CH:14][N:15]=2)[CH2:7]1.C1C=CC2N(O)N=[N:31]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:23][C:2]([F:24])([F:1])[C:3]1[CH:22]=[CH:21][CH:20]=[CH:19][C:4]=1[O:5][CH:6]1[CH2:10][CH2:9][N:8]([C:11]2[S:12][C:13]([C:16]([NH2:31])=[O:18])=[CH:14][N:15]=2)[CH2:7]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 684517792-{3-[2-(Trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carboxylic acid

Product 1

HCID 576528252-{3-[2-(Trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-{3-[2-(trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carboxylic acid (860 mg, 2.4 mmol), HOBt (324 mg, 2.4 mmol), HATU (1.5 g, 3.8 mmol) and NH4Cl (385 mg, 7.2 mmol) in DMF at rt was added DIPEA (2.1 mL, 12 mmol). The mixture was stirred at rt overnight. After dilution with water, the mixture was extracted twice with EtOAc. The EtOAc extracts were combined, washed twice with 0.5 N NaOH, diluted brine, 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): δ 7.79 (s, 1 H), 7.68-7.64 (m, 2 H), 7.39 (d, 1 H), 7.15 (t, 1 H), 5.48 (s, 1 H), 3.91 (m, 1 H), 3.78-3.62 (m, 4 H), 2.57-2.49 (m, 1 H), 2.44-2.40 (m, 1 H). MS (+ESI) m/z 358 (MH+).

Workup

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

Sources & evidence

ORD record
ord-62f70e8fa56c4ad78097c13c1e24fff9
Source dataset
uspto-grants-2010_07
Patent number
US07754745B2

Reaction notes

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