1-Methoxy-2-propanol → (2-Methoxy-4-morpholin-4-ylmethyl-phenyl)-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine

HRID 1262302Notes

Reaction equation

HRID 1262302 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:17]2[C:12]([CH:13]=[N:14][C:15](OS(C(F)(F)F)(=O)=O)=[N:16]2)=[CH:11][CH:10]=1.[CH3:26][O:27][C:28]1[CH:33]=[C:32]([CH2:34][N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)[CH:31]=[CH:30][C:29]=1[NH2:41].C(N(CC)C(C)C)(C)C.COCC(O)C.[O-]S(C(F)(F)F)(=O)=O>>[CH3:26][O:27][C:28]1[CH:33]=[C:32]([CH2:34][N:35]2[CH2:36][CH2:37][O:38][CH2:39][CH2:40]2)[CH:31]=[CH:30][C:29]=1[NH:41][C:15]1[N:14]=[CH:13][C:12]2=[CH:11][CH:10]=[C:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[O:2][CH3:1])[N:17]2[N:16]=1

Participants

6

Reactant 5

HCID 79001-Methoxy-2-propanolHCID 81531DiisopropylethylamineHCID 2758875TrifluoromethanesulfonateHCID 574160932-Methoxy-4-[(morpholin-4-yl)methyl]anilineHCID 86661678Trifluoro-methanesulfonic acid 7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester

Product 1

HCID 66712339(2-Methoxy-4-morpholin-4-ylmethyl-phenyl)-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine

Conditions

Temperature
120 °C

Procedure

Into a 8-dram vial, Trifluoro-methanesulfonic acid 7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester (72.9 mg, 0.195 mmol), 2-Methoxy-4-morpholin-4-ylmethyl-phenylamine (0.174 g, 0.782 mmol), N,N-Diisopropylethylamine (0.136 mL, 0.782 mmol), and 1-Methoxy-2-propanol (0.250 mL, 2.56 mmol). The reaction mixture was heated at 120° C. for 60 minutes. HPLC suggested little if any triflate SM. 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 (2-Methoxy-4-morpholin-4-ylmethyl-phenyl)-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine a brown solid (11 mg, 10%). LCMS (E/I+) 445.19 (M+H). NMR 1H (DMSO-d6)-9.81 (s, 1H), 8.99 (s, 1H), 8.24 (d, 1H, J=8.32 Hz), 7.73-7.82 (m, 2H), 7.48 (dt, 1H, JJ=1.19, 8.92 Hz), 7.22 (d, 1H, J=8.11 Hz), 7.17 (, s, 1H), 7.11 (t, 1H, J=7.40 Hz), 6.85-7.05 (m, 3H), 4.28 (bs, 2H), 3.90-4.02 (m, 5H), 3.79 (s, 3H), 3.62 (t, 2H, J=11.67 Hz), 3.26 (d, 2H, J=13.80 Hz), 3.08 (bs, 2H).

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-b6d80498c28646369a475fe28a6d75ed
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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