1-Methoxy-2-propanol → HCID 178491862, compound

HRID 1262320Notes

Reaction equation

HRID 1262320 reaction equation
[CH3:1][O:2][C:3]1[CH:9]=[C:8]([C@H:10]2[CH2:15][CH2:14][C@H:13]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[CH2:12][CH2:11]2)[CH:7]=[CH:6][C:4]=1[NH2:5].[CH3:22][O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]1[N:38]2[C:33]([CH:34]=[N:35][C:36](OS(C(F)(F)F)(=O)=O)=[N:37]2)=[CH:32][CH:31]=1.C(N(CC)C(C)C)(C)C.COCC(O)C>>[CH3:1][O:2][C:3]1[CH:9]=[C:8]([C@H:10]2[CH2:11][CH2:12][C@H:13]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[CH2:14][CH2:15]2)[CH:7]=[CH:6][C:4]=1[NH:5][C:36]1[N:35]=[CH:34][C:33]2=[CH:32][CH:31]=[C:30]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[O:23][CH3:22])[N:38]2[N:37]=1

Participants

5

Reactant 4

HCID 79001-Methoxy-2-propanolHCID 81531DiisopropylethylamineHCID 86661678Trifluoro-methanesulfonic acid 7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl esterHCID 178491861HCID 178491861, compound

Product 1

HCID 178491862HCID 178491862, compoundYield 48.7%

Conditions

Temperature
120 °C

Procedure

Into an 8-dram vial, 2-methoxy-4-[trans-4-(morpholin-4-yl)cyclohexyl]aniline (0.125 g, 0.430 mmol), Trifluoro-methanesulfonic acid 7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester (98 mg, 0.26 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-methoxy-4-[trans-4-(morpholin-4-yl)cyclohexyl]phenyl}-7-(2-methoxyphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine as a yellow solid (65 mg, 48%). LCMS (E/I+) 514.23 (M+H). NMR 1H (DMSO-d6)-9.71 (bs, 1H), 8.97 (s, 1H), 8.03 (d, 1H, J=8.03 Hz), 7.81 (d, 1H, J=7.74 Hz), 7.60 (s, 1H), 7.46 (t, 1H, J=7.74 Hz), 7.22 (d, 1H, J=8.32 Hz), 7.10 (t, 1H, J=7.74 Hz), 6.98 (d, 1H, J=4.64 Hz), 6.94 (d, 1H, J=4.64 Hz), 6.89 9 s, 1H), 6.69 (d, 1H, J=8.33 Hz), 4.02 (d, 2H, J=12.02 Hz), 3.87 (s, 3H), 3.79 (s, 3H), 3.70 (t, 2H, J=11.78 Hz), 3.46 (d, 2H, J=12.02v), 3.28 (bs, 1H), 3.15 (q, 2H, J=11.54 Hz), 1.97-2.10 (m, 4H), 1.47-1.64 (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-addca817217748768d139e229f0cc60f
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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