Ammonium Chloride → (Rac)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxamide, trifluoroacetate salt

HRID 2402394Notes

Reaction equation

HRID 2402394 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[OH:8][C:9]1([C:22]2[S:23][C:24]([C:27]3[CH:32]=[C:31]([CH3:33])[CH:30]=[C:29]([NH:34][C:35]4[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][N:36]=4)[N:28]=3)=[CH:25][N:26]=2)[CH2:18][CH2:17][CH2:16][C:15]2[CH:14]=[C:13]([C:19]([OH:21])=O)[CH:12]=[CH:11][C:10]1=2.[Cl-].[NH4+].F[P-](F)(F)(F)(F)F.[N:54]1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C=O)C.CS(C)=O>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[OH:8][C:9]1([C:22]2[S:23][C:24]([C:27]3[CH:32]=[C:31]([CH3:33])[CH:30]=[C:29]([NH:34][C:35]4[CH:40]=[C:39]([C:41]([F:43])([F:44])[F:42])[CH:38]=[CH:37][N:36]=4)[N:28]=3)=[CH:25][N:26]=2)[CH2:18][CH2:17][CH2:16][C:15]2[CH:14]=[C:13]([C:19]([NH2:54])=[O:21])[CH:12]=[CH:11][C:10]1=2

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131731736(Rac)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid, trifluoroacetate salt

Product 1

HCID 131731737(Rac)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxamide, trifluoroacetate saltYield 55.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (rac)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid, trifluoroacetate salt (50 mg, 0.078 mmol), ammonium chloride (62.6 mg, 1.171 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (44.5 mg, 0.117 mmol) in DMF (781 μL) was added diisopropylethylamine (40.9 μl, 0.234 mmol), and the reaction was heated at 50° C. for 16 h. The reaction mixture was then diluted with DMSO (1 mL), barrier filtered, and purified by reverse-phase HPLC (C18 column, water-acetonitrile, TFA modifier) to give (rac)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxamide, trifluoroacetate salt (27.4 mg, 0.043 mmol, 43% yield) as a yellow solid. MS ESI calcd for C26H22F3N5O2S [M+H]+ 526, found 526. 1H NMR (500 MHz, DMSO) δ 10.21 (s, 1H), 8.64 (s, 1H), 8.48 (s, 1H), 8.22 (s, 1H), 7.88 (s, 1H), 7.64 (s, 1H), 7.57 (s, 1H), 7.35 (s, 1H), 7.28 (s, 1H), 7.25 (d, J=8.2 Hz, 1H), 7.21 (d, J=4.5 Hz, 1H), 7.11 (s, 1H), 2.89-2.80 (m, 2H), 2.39-2.32 (m, 1H), 2.30 (s, 3H), 2.15-2.07 (m, 1H), 2.04-1.89 (m, 2H) ppm.

Workup

  1. filtrationfiltered
  2. custompurified by reverse-phase HPLC (C18 column, water-acetonitrile, TFA modifier)

Sources & evidence

ORD record
ord-418082e35b1c4896b15cbc0df3f08cd5
Source dataset
uspto-grants-2014_08
Patent number
US08796310B2

Reaction notes

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