p-Toluenesulfonic acid → HCID 58110105, compound

HRID 1803313Notes

Reaction equation

HRID 1803313 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[N:10]=[CH:11][N:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[N:38]=[C:24]4[CH:25]([C:31]5[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=5)[CH2:26]C(=O)[CH2:28][CH2:29][N:23]4[N:22]=3)=[CH:16][C:15]=2[O:39][CH3:40])[CH:13]=1.[CH:41]([O:46][CH3:47])([O:44][CH3:45])OC.S(O)(C1C=CC(C)=CC=1)(=O)=O>CO>[Cl:8][C:9]1[N:10]=[CH:11][N:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[N:38]=[C:24]4[CH:25]([C:31]5[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=5)[CH2:26][C:41]([O:44][CH3:45])([O:46][CH3:47])[CH2:28][CH2:29][N:23]4[N:22]=3)=[CH:16][C:15]=2[O:39][CH3:40])[CH:13]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 66860172HCID 66860172, compound

Product 1

HCID 58110105HCID 58110105, compoundYield 47.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-9-(4-fluorophenyl)-8,9-dihydro-5H-[1,2,4]triazolo[1,5-a]azepin-7(6H)-one (200 mg, 0.428 mmol, from example 137) in MeOH (2 mL) was added trimethyl orthoformate (0.469 mL, 4.28 mmol) followed by Ts-OH (8.15 mg, 0.043 mmol). The reaction mixture was stirred at room temperature for 16 h. The reaction was concentrated in vacuo. The crude product was purified using reverse phase preparatory HPLC (AcCN/water/ammonium acetate) to afford the titled compound (104 mg, 46% yield). LC-MS (M+H)+ 513.3. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.51 (1 H, d, J=1.5 Hz), 7.40 (1 H, d, J=2.4 Hz), 7.31-7.35 (2 H, m), 7.06-7.14 (3 H, m), 7.02 (1 H, d, J=1.5 Hz), 6.78 (1 H, dd, J=8.5, 2.4 Hz), 6.59 (1 H, s), 4.39 (1 H, ddd, J=14.7, 5.9, 2.3 Hz), 4.20-4.28 (1 H, m), 4.11-4.17 (1 H, m), 3.76 (3 H, s), 3.29 (3 H, s), 3.26 (3 H, s), 2.35-2.43 (2 H, m), 2.05-2.12 (1 H, m), 1.89 (1 H, ddd, J=14.5, 11.9, 2.3 Hz).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customThe crude product was purified

Sources & evidence

ORD record
ord-ebe568e317aa4ccf9aec7671d80dba12
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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