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

HRID 1262306Notes

Reaction equation

HRID 1262306 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.[CH2:38]1[O:41][C@H:39]1[CH3:40]>CO>[OH:41][C@@H:39]([CH3:40])[CH2:38][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 146262(2S)-2-MethyloxiraneHCID 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 66712138N-[2-(2-{4-[4-((S)-2-Hydroxy-propyl)-piperazin-1-ylmethyl]-2-methoxy-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamideYield 17.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Into a 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 mg, 0.1 mmol), Methanol (5 mL) and (S)-(−)-Propylene Oxide (0.00818 g, 0.141 mmol) were added. The reaction was stirred at room temperature over the weekend. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions were lyophilized to give N-[2-(2-{4-[4-((S)-2-Hydroxy-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 (10 mg, 11%). LCMS (E/I+) 580.13 (M+H). NMR 1H (DMSO-d6)-8.99 (s, 1H), 8.05 (d, 1H, J=7.67 Hz), 7.96-8.01 (m, 1H), 7.80 (s, 1H), 7.64-7.69 (m, 1H), 7.52-7.58 (m, 2H), 7.80 (bs, 1H), 7.03 (d, 1H, J=4.69 Hz), 7.00 (d, 1H, J=4.69 Hz), 6.87 (bd, 1H, J=7.39 Hz), 4.00 (bs, 2H), 3.88 (s, 3H), 2.50-3.70 (bm, 17H), 1.05 (bs, 3H).

Workup

  1. customThe reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN

Sources & evidence

ORD record
ord-4b7fd518a4f94b9291a966627562c60f
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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