Trifluoroacetic acid → HCID 58110188, compound

HRID 1803310Notes

Reaction equation

HRID 1803310 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[CH2:44][CH2:43][CH2:42]1.C([BH3-])#N.[Na+].C(O)(C(F)(F)F)=O>C(O)C>[N:41]1([CH:27]2[CH2:28][CH2:29][N:23]3[N:22]=[C:21]([NH:20][C:17]4[CH:18]=[CH:19][C:14]([N:12]5[CH:13]=[C:9]([Cl:8])[N:10]=[CH:11]5)=[C:15]([O:39][CH3:40])[CH:16]=4)[N:38]=[C:24]3[CH:25]([C:31]3[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=3)[CH2:26]2)[CH2:44][CH2:43][CH2:42]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10422AzetidineHCID 5003444Sodium cyanoborohydrideHCID 66860172HCID 66860172, compound

Product 1

HCID 58110188HCID 58110188, compoundYield 34.4%

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 azetidine (6.11 mg, 0.107 mmol), and sodium cyanoborohydride (1.0M in THF, 428 μL, 0.428 mmol) in ethanol (0.535 mL). The mixture was stirred at rt for 16 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 (18.7 mg, 27% yield) as a TFA salt. LC-MS (M+H)+ 508.3. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.63 (1 H, d, J=3.7 Hz), 7.89-7.98 (1 H, m), 7.31-7.38 (1 H, m), 7.07-7.22 (5 H, m), 7.01 (2 H, dd, J=8.5, 4.9 Hz), 4.92 (2 H, d, J=4.6 Hz), 4.64-4.77 (1 H, m), 4.42 (2 H, br. s.), 3.98-4.10 (1 H, m), 3.66-3.97 (5 H, m), 2.58-2.90 (2 H, m), 2.14-2.44 (4 H, m).

Workup

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

Sources & evidence

ORD record
ord-427c6313e95e4ec1be6740542b7594e2
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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