1-Methoxy-2-propanol → (4-{3-Methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetic acid tert-butyl ester

HRID 1262348Notes

Reaction equation

HRID 1262348 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.[C:26]([O:30][C:31](=[O:48])[CH2:32][N:33]1[CH2:38][CH2:37][CH:36]([C:39]2[CH:44]=[CH:43][C:42]([NH2:45])=[C:41]([O:46][CH3:47])[CH:40]=2)[CH2:35][CH2:34]1)([CH3:29])([CH3:28])[CH3:27].C(N(CC)C(C)C)(C)C.COCC(O)C>>[C:26]([O:30][C:31](=[O:48])[CH2:32][N:33]1[CH2:34][CH2:35][CH:36]([C:39]2[CH:44]=[CH:43][C:42]([NH:45][C:15]3[N:14]=[CH:13][C:12]4=[CH:11][CH:10]=[C:9]([C:4]5[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=5[O:2][CH3:1])[N:17]4[N:16]=3)=[C:41]([O:46][CH3:47])[CH:40]=2)[CH2:37][CH2:38]1)([CH3:29])([CH3:28])[CH3:27]

Participants

5

Reactant 4

HCID 79001-Methoxy-2-propanolHCID 81531DiisopropylethylamineHCID 66711699[4-(4-Amino-3-methoxy-phenyl)-piperidin-1-yl]-acetic acid tert-butyl esterHCID 86661678Trifluoro-methanesulfonic acid 7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester

Product 1

HCID 66712696(4-{3-Methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetic acid tert-butyl ester

Conditions

Temperature
80 °C

Procedure

Into an 8-dram vial Trifluoro-methanesulfonic acid 7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester (100 mg, 0.3 mmol), [4-(4-Amino-3-methoxy-phenyl)-piperidin-1-yl]-acetic acid tert-butyl ester (133 mg, 0.415 mmol), N,N-Diisopropylethylamine (150 uL, 0.86 mmol) and 1-Methoxy-2-propanol (2 mL, 20 mmol) were added. The reaction mixture was heated at 80° C. After 3 days, solvent was removed and the product, (4-{3-Methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetic acid tert-butyl ester, was purified by flash chromatography (ISCO, 40 g column, hexane; EtOAc 1:1) as a gum (79 mg, 54%). LCMS (E/I+) 544 (M+H). NMR 1H (MeOH-d4)-8.7 (s, 1H), 8.16 (d, 1H, J=8.28 Hz), 7.82 (d, 1H, J=7.56 Hz), 7.45 (m, 1H), 7.16 (d, 1H, J=8.32 Hz), 7.09 (m, 1H), 6.95 (d, 1H, J=4.67 Hz), 6.89 (d, 1H, J=4.68 Hz), 6.81 (s, 1H), 6.72 (s, 1H), 6.63 (m, 1H), 3.89 (s, 3H), 3.83 (s, 2H), 3.80 (s, 3H), 3.03 (m, 2H), 2.43 (m, 1H), 2.25 (m, 2H), 1.76 (m, 4H), 1.49 (s, 9H).

Workup

  1. customsolvent was removed
  2. customthe product, (4-{3-Methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetic acid tert-butyl ester, was purified by flash chromatography (ISCO, 40 g column, hexane; EtOAc 1:1) as a gum (79 mg, 54%)

Sources & evidence

ORD record
ord-34e07bbc927547a99f1aae3c888f74aa
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

Loading…