Methanesulfonic Acid → HCID 66710944, compound

HRID 1262127Notes

Reaction equation

CS([C:4]1[N:9]=[CH:8][C:7]2=[CH:10][CH:11]=[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][CH3:20])[N:6]2[N:5]=1)=O.CS(O)(=O)=O.[NH2:26][C:27]1[CH:32]=[CH:31][C:30]([CH:33]2[CH2:38][CH2:37][N:36]([CH2:39][C@H:40]([OH:45])[C:41]([F:44])([F:43])[F:42])[CH2:35][CH2:34]2)=[CH:29][C:28]=1[O:46][CH3:47].FC(F)(F)C(O)=O>COCC(O)C>[F:44][C:41]([F:42])([F:43])[C@@H:40]([OH:45])[CH2:39][N:36]1[CH2:35][CH2:34][CH:33]([C:30]2[CH:31]=[CH:32][C:27]([NH:26][C:4]3[N:9]=[CH:8][C:7]4=[CH:10][CH:11]=[C:12]([C:13]5[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=5[O:19][CH3:20])[N:6]4[N:5]=3)=[C:28]([O:46][CH3:47])[CH:29]=2)[CH2:38][CH2:37]1

Participants

Conditions

Temperature: 135 °C

Procedure

2-Methanesulfinyl-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazine (50.00 mg, 0.174 mmol), methanesulfonic acid (0.034 mL, 0.52 mmol) and (S)-3-[4-(4-amino-3-methoxy-phenyl)-piperidin-1-yl]-1,1,1-trifluoro-propan-2-ol (109 mg, 0.342 mmol) were combined in 1-methoxy-2-propanol (1.02 mL) in a capped tube and the reaction was stirred at 135° C. for 48 h. The product was isolated by reverse phase preparative hplc (Gilson) followed by neutralization of the trifluoroacetic acid salt to afford (S)-1,1,1-trifluoro-3-(4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-propan-2-ol as a brown solid (17 mg, 18%). MP: 77-94° C.; 1H-NMR (CDCl3) δ 8.69 (s, 1H), 8.30 (d, J=8.1 Hz, 1H), 7.99 (d, J=7.6 Hz, 1H), 7.44 (m, 2H), 7.14 (m, 1H), 7.08 (d, J=8.4 Hz, 1H), 7.02 (4.4 Hz, 1H), 6.83 (d, J=4.5 Hz, 1H), 6.71 (m, 2H), 4.08 (m, 1H), 3.90 (s, 3H), 3.85 (s, 3H), 3.02 (m, 2H), 2.67 (m, 2H), 2.52 (m, 2H), 2.23 (m, 1H), 1.77 (m, 3H); LC/MS (ESI+): 542.3 (M+H).

Workup

customThe product was isolated by reverse phase preparative hplc (Gilson)

Sources & evidence

ORD record: ord-f65c372a9d5447088b20ae4f83c0971a
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08471005B2

Reaction notes

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