Cyclohexanecarboxylic acid → HCID 3010846, compound

HRID 1595270Notes

Reaction equation

HRID 1595270 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:24])[CH2:15][NH:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:9][CH:8]=2)[N:6]=1.[CH:25]1([C:31]([OH:33])=O)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:24])[CH2:15][N:16]([CH2:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:31]([CH:25]3[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]3)=[O:33])=[CH:9][CH:8]=2)[N:6]=1

Participants

7

Reactant 4

HCID 7413Cyclohexanecarboxylic acidHCID 81531DiisopropylethylamineHCID 491938Acetamide, N-[4-(2-amino-4-thiazolyl)phenyl]-2-[(phenylmethyl)amino]-HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate

Product 1

HCID 3010846HCID 3010846, compoundYield 73.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-{4-(2-amino-4-thiazolyl)phenyl}-2-{(phenylmethyl)amino}acetamide (352 mg, 1.04 mmol, described in example 2), cyclohexanecarboxylic acid (140 mg, 1.09 mmol) and DIPEA (269 mg, 2.08 mmol) in DMF (5.2 mL) was added TBTU (350 mg, 1.09 mmol). The mixture was stirred at room temperature for 6 h. The reaction mixture was diluted with EtOAc (125 mL). The resulting solution was washed with saturated aqueous NaHCO3 (40 mL), H2O (40 mL), and brine (40 mL), then dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO2, CHCl3:EtOH, 15:1) to yield the title compound (341 mg, 73% yield) as a white solid: M.p. 214.5-215.5°; 1H NMR (400 MHz, DMSO-d6) δ(2 rotamers, 1:1) 10.06, 9.92 (2 s,1H), 7.73, 7.71 (2 d, J=8.5 Hz, 2H), 7.56, 7.55 (2 d, J=8.5 Hz, 2H), 7.20-7.41 (m, 5H), 7.01, 7.00 (2 s, 2H), 6.89, 6.88 (2 s, 1H), 4.70, 4.51 (2 s, 2H), 4.13, 4.02 (2 s, 2H), 2.64, 2.56 (2 broad t, J=10.5 Hz, 1H), 1.61-1.70 (m, 5H), 1.12-1.46 (m, 5H); MS (FAB) m/z 449 (MH)+; Anal. Calcd for C25H28N4O2S: C, 66.94; H, 6.29; N, 12.49. Found: C, 66.54; H, 6.29; N, 12.32.

Workup

  1. washThe resulting solution was washed with saturated aqueous NaHCO3 (40 mL), H2O (40 mL), and brine (40 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash chromatography (SiO2, CHCl3:EtOH, 15:1)

Sources & evidence

ORD record
ord-152cd04478114e71bd154c11fcc49c70
Source dataset
uspto-grants-2001_09
Patent number
US06288091B1

Reaction notes

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