1-Methoxy-2-propanol → N-(2-{2-[4-(4-Hydroxy-piperidin-1-ylmethyl)-2-methoxy-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-N-methyl-methanesulfonamide

HRID 1262313Notes

Reaction equation

HRID 1262313 reaction equation
[NH2:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9][CH2:8]2)=[CH:4][C:3]=1[O:16][CH3:17].[CH3:18][S:19]([N:22]([CH3:46])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]1[N:37]2[C:32]([CH:33]=[N:34][C:35](OS(C(F)(F)F)(=O)=O)=[N:36]2)=[CH:31][CH:30]=1)(=[O:21])=[O:20].C(N(CC)C(C)C)(C)C.COCC(O)C>>[OH:13][CH:10]1[CH2:11][CH2:12][N:7]([CH2:6][C:5]2[CH:14]=[CH:15][C:2]([NH:1][C:35]3[N:34]=[CH:33][C:32]4=[CH:31][CH:30]=[C:29]([C:24]5[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=5[N:22]([CH3:46])[S:19]([CH3:18])(=[O:21])=[O:20])[N:37]4[N:36]=3)=[C:3]([O:16][CH3:17])[CH:4]=2)[CH2:8][CH2:9]1

Participants

5

Reactant 4

HCID 79001-Methoxy-2-propanolHCID 81531DiisopropylethylamineHCID 574161131-[(4-Amino-3-methoxyphenyl)methyl]piperidin-4-olHCID 86661681Trifluoro-methanesulfonic acid 7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester

Product 1

HCID 66712457N-(2-{2-[4-(4-Hydroxy-piperidin-1-ylmethyl)-2-methoxy-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-N-methyl-methanesulfonamide

Conditions

Temperature
120 °C

Procedure

Into an 8-dram vial, [1-(4-Amino-3-methoxy-benzyl)-piperidin-4-ol (0.102 g, 0.430 mmol), Trifluoro-methanesulfonic acid 7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester (88.0 mg, 0.195 mmol), N,N-Diisopropylethylamine (0.0749 mL, 0.430 mmol), and 1-Methoxy-2-propanol (0.70 mL, 7.2 mmol) were added. The reaction mixture was heated at 120° C. for 6 hours. 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 collected fractions were lyophilized to give N-(2-{2-[4-(4-Hydroxy-piperidin-1-ylmethyl)-2-methoxy-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-N-methyl-methanesulfonamide a yellow solid (92 mg, 72%). LCMS (E/I+) 537.11 (M+H). NMR 1H (DMSO-d6)-9.16 (bs, 1H), 9.00 (s, 1H), 8.07-8.12 (m, 1H), 7.95-8.01 (m, 1H), 7.86 (s, 1H), 7.64-7.70 (m, 1H), 7.52-7.58 (m, 1H), 7.19 (d, 1H, J=9.96 Hz), 7.03 (d, 1H, J=4.60 Hz), 7.01 (d, 1H, J=4.60 Hz), 6.90-7.00 (m, 1H), 4.24 (dd, 2H, J=4.64, 16.65 Hz), 2.80-4.00 (m, 15H), 1.40-2.00 (m, 4H).

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

Sources & evidence

ORD record
ord-7800648e90e84d02b951c933ba183ede
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

Loading…