Hydrochloric Acid → HCID 118114706, compound

HRID 1050616Notes

Reaction equation

HRID 1050616 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[N:11]=[C:12]([N:19]3[CH2:24][CH2:23][CH2:22][C@@H:21]([NH:25][C:26](=[O:36])[C:27]4[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH3:35])=[CH:29][CH:28]=4)[CH2:20]3)[N:13]=[N:14][C:15]=2[C:16]([NH2:18])=[O:17])=[CH:5][CH:4]=1)#[N:2].Cl.[CH3:38][OH:39]>>[C:16]([C:15]1[N:14]=[N:13][C:12]([N:19]2[CH2:24][CH2:23][CH2:22][C@@H:21]([NH:25][C:26](=[O:36])[C:27]3[CH:28]=[CH:29][C:30]([O:33][CH2:34][CH3:35])=[CH:31][CH:32]=3)[CH2:20]2)=[N:11][C:10]=1[NH:9][C:6]1[CH:5]=[CH:4][C:3]([C:1](=[NH:2])[O:39][CH3:38])=[CH:8][CH:7]=1)(=[O:17])[NH2:18]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 118114478HCID 118114478, compound

Product 1

HCID 118114706HCID 118114706, compound

Procedure

(R)-5-(4-Cyanophenylamino)-3-(3-(4-ethoxybenzamido)piperidin-1-yl)-1,2,4-triazine-6-carboxamide (194) (90 mg, 0.18 mmol) was dissolved in 25 mL dry MeOH. It was chilled in an ice bath, and was then charged with HCl gas from a lecture bottle using a long needle to bubble the gas into the bottom of the solution until saturation reached. The resulting mixture was stirred at RT for overnight, and was placed back to the ice bath for repeated HCl gas charging till saturation. The resulting mixture was stirred for another overnight, and concentrated in vacuo to dryness to afford crude (R)-methyl 4-(6-carbamoyl-3-(3-(4-ethoxybenzamido)piperidin-1-yl)-1,2,4-triazin-5-ylamino)benzimidate (501). It was dissolved in 15 mL dry MeOH. To it was added dimethylamine (2M in THF, 1.0 mL). The mixture was sent to 60° C. bath and stirred for 1 hour. It was cooled to RT, concentrated in vacuo, acidified with 0.3 mL TFA, and directly subjected to reverse phase prep HPLC using 5 mM HCl (aq) and next MeCN as mobile phases to isolate the title compound, (R)-5-(4-(N,N-dimethylcarbamimidoyl)phenylamino)-3-(3-(4-ethoxybenzamido)piperidin-1-yl)-1,2,4-triazine-6-carboxamide (502), as HCl salt (59 mg). LC-MS (ESI): m/z (M+1) 532.2. UV: λ=267 nm.

Workup

  1. temperatureIt was chilled in an ice bath
  2. customto bubble the gas into the bottom of the solution until saturation
  3. stirringThe resulting mixture was stirred for another overnight
  4. concentrationconcentrated in vacuo to dryness

Sources & evidence

ORD record
ord-bc7c151b948f4da3b97ab06c40dbc744
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

Loading…