Trifluoroacetic acid → HCID 58110140, compound

HRID 1803311Notes

Reaction equation

HRID 1803311 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:27](=O)[CH2:28][CH2:29][N:23]4[N:22]=3)=[CH:16][C:15]=2[O:39][CH3:40])[CH:13]=1.[NH:41]1[CH2:45][CH2:44][CH2:43][CH2:42]1.C([BH3-])#N.[Na+].C(O)(C(F)(F)F)=O>C(O)C>[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:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=5)[CH2:26][CH:27]([N:41]5[CH2:45][CH2:44][CH2:43][CH2:42]5)[CH2:28][CH2:29][N:23]4[N:22]=3)=[CH:16][C:15]=2[O:39][CH3:40])[CH:13]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 31268PyrrolidineHCID 5003444Sodium cyanoborohydrideHCID 66860172HCID 66860172, compound

Product 1

HCID 58110140HCID 58110140, compoundYield 44.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

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 (50 mg, 0.107 mmol, from example 137) was added to a mixture of pyrrolidine (7.62 mg, 0.107 mmol), and sodium cyanoborohydride (1.0 M in THF, 428 μL, 0.428 mmol) in ethanol (0.535 mL). The mixture was stirred at rt for 48 h and then concentrated in vacuo. The crude product was purified using reverse phase preparatory HPLC (MeOH/water/trifluoroacetic acid) to afford the titled compound (24.8 mg, 35% yield) as a TFA salt. LC-MS (M+H)+ 522.4. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.80 (1 H, d, J=1.5 Hz), 7.35 (1 H, d, J=2.1 Hz), 6.98-7.22 (7 H, m), 4.96 (1 H, br. s.), 4.65-4.74 (1 H, m), 3.97-4.09 (1 H, m), 3.78-3.97 (5 H, m), 3.38 (1 H, br. s.), 2.92-3.02 (1 H, m), 2.84 (2 H, d, J=4.9 Hz), 2.36-2.53 (2 H, m), 2.03-2.31 (5 H, m).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe crude product was purified

Sources & evidence

ORD record
ord-98c8fbd8d9ec4a17a82bcc039c44706e
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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