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

HRID 1262307Notes

Reaction equation

HRID 1262307 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.[CH3:38][O:39][CH2:40][C@H:41]1[CH2:43][O:42]1>CO>[OH:42][C@@H:41]([CH2:40][O:39][CH3:38])[CH2:43][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 2

HCID 2734441(2R)-2-(Methoxymethyl)oxiraneHCID 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 66711645N-[2-(2-{4-[4-((R)-2-Hydroxy-3-methoxy-propyl)-piperazin-1-ylmethyl]-2-methoxy-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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 (70.0 mg, 0.134 mmol), (R)-2-Methoxymethyl-oxirane (0.0154 g, 0.174 mmol), and Methanol (5.00 mL) 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-Hydroxy-3-methoxy-propyl)-piperazin-1-ylmethyl]-2-methoxy-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide a yellow solid (32 mg, 39%). LCMS (E/I+) 610.15 (M+H). NMR 1H (DMSO-d6)-8.95 (s, 1H), 7.92-7.98 (m, 1H), 7.88 (d, 1H, J=8.26 Hz), 7.72 (s, 1H), 7.60-7.67 (m, 1H), 7.50-7.78 (m, 2H), 7.00 (d, 1H, J=4.66 Hz), 6.96 (d, 1H, J=4.66 Hz), 6.92 bs, 1H), 6.72 (d, 1H, J=8.26), 4.47 (bs, 1H), 3.82 (s, 3H) 3.71 (bs, 1H), 3.39 (bs, 2H), 3.25-3.31 (m, 2H), 3.24 (s, 3H), 3.17-3.23 (m, 1H) 3.04 (s, 3H), 2.88 (s, 3H), 2.20-2.42 (m, 9H).

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-c3c6328b566b4af1ba19038e1b14828d
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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