(S)-1-[4-(4-Amino-3-methoxy-phenyl)-piperazin-1-yl]-propan-2-ol → (S)-1-(4-{4-[7-(2-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxy-phenyl}-piperazin-1-yl)-propan-2-ol

HRID 1262086Notes

Reaction equation

HRID 1262086 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C@@H:15]([OH:17])[CH3:16])[CH2:10][CH2:9]2)=[CH:4][C:3]=1[O:18][CH3:19].CS([C:23]1[N:28]=[CH:27][C:26]2=[CH:29][CH:30]=[C:31]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[S:38]([CH3:41])(=[O:40])=[O:39])[N:25]2[N:24]=1)=O>>[CH3:41][S:38]([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=1[C:31]1[N:25]2[C:26]([CH:27]=[N:28][C:23]([NH:1][C:2]3[CH:7]=[CH:6][C:5]([N:8]4[CH2:13][CH2:12][N:11]([CH2:14][C@@H:15]([OH:17])[CH3:16])[CH2:10][CH2:9]4)=[CH:4][C:3]=3[O:18][CH3:19])=[N:24]2)=[CH:29][CH:30]=1)(=[O:39])=[O:40]

Participants

3

Reactant 2

HCID 66711198(S)-1-[4-(4-Amino-3-methoxy-phenyl)-piperazin-1-yl]-propan-2-olHCID 667114062-Methanesulfinyl-7-(2-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 66711407(S)-1-(4-{4-[7-(2-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxy-phenyl}-piperazin-1-yl)-propan-2-ol

Conditions

Temperature
190 °C

Procedure

Following the procedure of example 532 (c), (S)-1-[4-(4-Amino-3-methoxy-phenyl)-piperazin-1-yl]-propan-2-ol (0.087 g, 0.33 mmol) and 2-Methanesulfinyl-7-(2-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazine (0.16 g, 0.48 mmol) were heated in the microwave at 190° C. for 4 hours. Purification by Gilson chromatography gave (S)-1-(4-{4-[7-(2-Methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxy-phenyl}-piperazin-1-yl)-propan-2-ol as a tan solid. MP: 98-100° C.; LCMS (m/e) 537 (M+1); 1H-NMR (DMSO-d6, 400 MHz) δ 8.94 (s, 1H), 8.16-8.15 (d, 1H, J=6.84 Hz), 7.88-7.85 (t, 1H, J=6.24 Hz), 7.80-7.76 (t, 1H, J=7.73 Hz), 7.70-7.68 (d, 1H, J=7.56 Hz), 7.60 (s, 1H), 7.44-7.42 (d, 1H, J=8.77 Hz), 6.95-6.91 (q, 2H, J=4.64 Hz), 6.56 (s, 1H), 6.21-6.18 (dd, 1H, J=2.44 Hz), 4.30-4.29 (d, 1H), 3.77 (s, 3H), 3.29 (s, 1H), 3.05-3.03 (m, 3H), 2.87 (s, 3H), 2.55-2.52 (m, 2H), 2.28-2.21 (m, 6H).

Workup

  1. customPurification by Gilson chromatography

Sources & evidence

ORD record
ord-d7115e2ebaca4e3590eb17a8d371637b
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

Loading…