Methanol → N-[2-(2-{4-[4-((R)-2,3-Dihydroxy-propyl)-piperazin-1-ylmethyl]-2-methoxy-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide

HRID 1262308Notes

Reaction equation

HRID 1262308 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:6]=[CH:5][C:4]=1[NH:16][C:17]1[N:22]=[CH:21][C:20]2=[CH:23][CH:24]=[C:25]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[N:32]([CH3:37])[S:33]([CH3:36])(=[O:35])=[O:34])[N:19]2[N:18]=1.[O:38]1[CH2:40][C@H:39]1[CH2:41][OH:42].CO>>[OH:38][C@@H:39]([CH2:41][OH:42])[CH2:40][N:13]1[CH2:14][CH2:15][N:10]([CH2:9][C:7]2[CH:6]=[CH:5][C:4]([NH:16][C:17]3[N:22]=[CH:21][C:20]4=[CH:23][CH:24]=[C:25]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=5[N:32]([CH3:37])[S:33]([CH3:36])(=[O:35])=[O:34])[N:19]4[N:18]=3)=[C:3]([O:2][CH3:1])[CH:8]=2)[CH2:11][CH2:12]1

Participants

4

Reactant 3

HCID 887MethanolHCID 5460455(+)-GlycidolHCID 66711969N-{2-[2-(2-Methoxy-4-piperazin-1-ylmethyl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-phenyl}-N-methyl-methanesulfonamide

Product 1

HCID 66712706N-[2-(2-{4-[4-((R)-2,3-Dihydroxy-propyl)-piperazin-1-ylmethyl]-2-methoxy-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamideYield 21%

Procedure

Into an 8-dram vial, N-{2-[2-(2-Methoxy-4-piperazin-1-ylmethyl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-phenyl}-N-methyl-methanesulfonamide (80 mg, 0.2 mmol), (R)-Oxiranemethanol (0.0350 g, 0.472 mmol), and Methanol (5.87 mL, 145 mmol) were added. The reaction was stirred at room temperature over the weekend. The solvent was removed under vacuum. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The selected fractions were concentrated. The residue was partitioned with DCM and sat. NaHCO3. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered wand washed with DCM. The solvent was removed under vacuum to give N-[2-(2-{4-[4-((R)-2,3-Dihydroxy-propyl)-piperazin-1-ylmethyl]-2-methoxy-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide as a yellow solid (20 mg, 21%). LCMS (E/I+) 596.11 (M+H). NMR 1H (DMSO-d6)-8.97 (s, 1H), 7.90-7.98 (m, 1H), 7.88 (d, 1H, J=8.21 Hz), 7.72 (s, 1H), 7.62-7.66 (m, 1H), 7.51-7.56 (m, 1H), 7.00 (d, 1H, J=4.67 Hz), 6.96 (d, 1H, J=4.67 Hz), 6.92 (bs, 1H), 6.72 (d, 1H, J=8.01 Hz), 4.51 (t, 1H, J=5.55), 4.34 (d, 1H, J=4.34 Hz), 3.82 (s, 3H), 2.18-3.70 (bm, 21H).

Workup

  1. customThe solvent was removed under vacuum
  2. customThe reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN
  3. concentrationThe selected fractions were concentrated
  4. customThe residue was partitioned with DCM and sat. NaHCO3
  5. customThe organic was separated
  6. washwashed with Brine
  7. dry with materialdried over Na2SO4
  8. filtrationThe solid was filtered
  9. washwand washed with DCM
  10. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-68ad0297bf5a4942923100ddb65ff86b
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

Loading…