Dimethylamine → HCID 58110141, compound

HRID 1803309Notes

Reaction equation

HRID 1803309 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.[CH3:41][NH:42][CH3:43].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:42]([CH3:43])[CH3:41])[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 674DimethylamineHCID 6422Trifluoroacetic acidHCID 5003444Sodium cyanoborohydrideHCID 66860172HCID 66860172, compound

Product 1

HCID 58110141HCID 58110141, compoundYield 56.1%

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 (100 mg, 0.214 mmol, from example 137) was added to a mixture of dimethylamine (2M in THF, 1.07 mL, 2.14 mmol), and sodium cyanoborohydride (1.0 M in THF, 857 μL, 0.857 mmol) in ethanol (1.1 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 (59.5 mg, 43% yield) as a TFA salt. LC-MS (M+H)+ 496.2. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.90-7.99 (1 H, m), 7.32-7.39 (1 H, m), 7.19-7.25 (1 H, m), 7.09-7.17 (4 H, m), 6.91-7.04 (2 H, m), 4.99 (1 H, br. s.), 4.70 (1 H, ddd, J=15.2, 5.3, 2.4 Hz), 4.03 (1 H, dd, J=14.2, 12.1 Hz), 3.86-3.97 (3 H, m), 3.39-3.55 (1 H, m), 3.03 (1 H, dd, J=13.9, 5.6 Hz), 2.74-2.88 (6 H, m), 2.52 (1 H, br, s.), 2.17-2.33 (1 H, m), 1.97-2.13 (1 H, m), 1.37-1.51 (1 H, m).

Workup

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

Sources & evidence

ORD record
ord-be6eeec07d764cdba82d66395a92bd44
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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