Trifluoroacetic acid → HCID 58456274, compound

HRID 410552Notes

Reaction equation

HRID 410552 reaction equation
C1C2C(OC([NH:17][C:18]3([C:48]([OH:50])=[O:49])[CH2:23][CH2:22][C:21]([OH:47])([C:24]4[S:25][C:26]([C:29]5[CH:34]=[C:33]([NH:35][C:36]6[N:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[CH:38][N:37]=6)[CH:32]=[C:31]([CH3:46])[CH:30]=5)=[CH:27][N:28]=4)[CH2:20][CH2:19]3)=O)C3C(=CC=CC=3)C=2C=CC=1.N1CCCCC1.C(O)(C(F)(F)F)=O>CN(C=O)C>[NH2:17][C:18]1([C:48]([OH:50])=[O:49])[CH2:23][CH2:22][C:21]([OH:47])([C:24]2[S:25][C:26]([C:29]3[CH:34]=[C:33]([NH:35][C:36]4[N:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[CH:38][N:37]=4)[CH:32]=[C:31]([CH3:46])[CH:30]=3)=[CH:27][N:28]=2)[CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 8082PiperidineHCID 67433394HCID 67433394, compound

Product 1

HCID 58456274HCID 58456274, compoundYield 9.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-{[(9H-Fluoren-9-yloxy)carbonyl]amino}-4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylic acid (0.079 g, 0.11 mmol) was dissolved in DMF (1.0 mL). Piperidine (0.086 g, 1.01 mmol) was added. After 15 minutes, the reaction mixture was directly purified by reverse phase HPLC to yield 1-amino-4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylic acid (0.005 g, 0.01 mmol) as its TFA salt. MS ESI: [M+H]+ m/z 494.1. 1H NMR (600 MHz, CD3OD) δ 8.70 (d, J=4.9, 1H), 8.04 (s, 1H), 7.94-7.80 (m, 2H), 7.69 (d, J=7.6, 1H), 7.52-7.42 (m, 1H), 7.42-7.34 (m, 1H), 7.18-7.00 (m, 2H), 2.60-2.42 (m, 2H), 2.36 (s, 3H), 2.28-2.07 (m, 4H), 2.05-1.89 (m, 2H). rhSYK activity=+++. The starting material was prepared generally following the procedures described in Examples 32 and 33 using commercially available 1-{[{9H-fluoren-9-ylmethoxy)carbonyl]amino}-4-oxocyclohexanecarboxylic acid.

Workup

  1. customthe reaction mixture was directly purified by reverse phase HPLC

Sources & evidence

ORD record
ord-304fa3c082bb472e92df18ae6674be84
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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