2-[4-(4-Amino-2-methoxy-phenyl)-piperidin-1-yl]-acetamide → 2-(4-{2-Methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetamide

HRID 1262145Notes

Reaction equation

HRID 1262145 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.[NH2:26][C:27]1[CH:32]=[CH:31][C:30]([CH:33]2[CH2:38][CH2:37][N:36]([CH2:39][C:40]([NH2:42])=[O:41])[CH2:35][CH2:34]2)=[C:29]([O:43][CH3:44])[CH:28]=1>>[CH3:44][O:43][C:29]1[CH:28]=[C:27]([NH:26][C:15]2[N:14]=[CH:13][C:12]3=[CH:11][CH:10]=[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])[N:17]3[N:16]=2)[CH:32]=[CH:31][C:30]=1[CH:33]1[CH2:38][CH2:37][N:36]([CH2:39][C:40]([NH2:42])=[O:41])[CH2:35][CH2:34]1

Participants

3

Reactant 2

HCID 667119832-[4-(4-Amino-2-methoxy-phenyl)-piperidin-1-yl]-acetamideHCID 86661678Trifluoro-methanesulfonic acid 7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester

Product 1

HCID 667119392-(4-{2-Methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetamideYield 33.7%

Procedure

Trifluoro-methanesulfonic acid 7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester (0.100 g, 0.268 mmol) and 2-[4-(4-Amino-2-methoxy-phenyl)-piperidin-1-yl]-acetamide (0.0882 g, 0.335 mmol) were reacted in an analogous manner to Example 908D at 50° C. for 16 h. The reaction mixture was concentrated, taken up in EtOAc, and washed with brine. The EtOAc layer was dried, filtered over MgSO4, and concentrated. The resulting residue was purified by Gilson RP-HPLC and lyophilized. The product was taken up in EtOAc and washed with NaHCO3 to free-base it to afford title compound (44 mg, 32%). LCMS=487.0 (M+H), HPLC rt=2.500, purity=98%. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.29 (s, 1H), 8.94 (s, 1H), 7.70 (d, J=7.3 Hz, 1H), 7.45 (dd, J=7.3, 7.7 Hz, 1H), 7.37 (s, 1H), 7.19 (d, J=8.3 Hz, 2H), 7.08 (d, J=7.4 Hz, 1H), 6.97 (d, J=8.3 Hz, 1H0, 6.91 (d, J=4.3 Hz, 1H), 6.88 (d, J=4.3 Hz, 1H), 3.76 (s, 3H), 3.42 (s, 3H), 3.31 (s, 2H), 2.89-2.82 (m, 3H), 2.80-2.68 (m, 1H), 2.20-2.05 (m, 2H), 1.72-1.58 (m, 4H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. washwashed with brine
  3. dry with materialThe EtOAc layer was dried
  4. filtrationfiltered over MgSO4
  5. concentrationconcentrated
  6. customThe resulting residue was purified by Gilson RP-HPLC
  7. washwashed with NaHCO3 to free-base it

Sources & evidence

ORD record
ord-deee6ee85cb14ff0b471e6fa7500a6e2
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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