1-Methoxy-2-propanol → HCID 66711981, compound

HRID 1262310Notes

Reaction equation

[NH2:1][C:2]1[C:3]([O:17][CH3:18])=[C:4]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]2)=[O:9])[CH:5]=[CH:6][CH:7]=1.[CH3:19][S:20]([N:23]([CH3:47])[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)(=[O:22])=[O:21].C(N(CC)C(C)C)(C)C.COCC(O)C>>[CH3:18][O:17][C:3]1[C:4]([C:8]([N:10]2[CH2:11][CH2:12][N:13]([CH3:16])[CH2:14][CH2:15]2)=[O:9])=[CH:5][CH:6]=[CH:7][C:2]=1[NH:1][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[N:23]([CH3:47])[S:20]([CH3:19])(=[O:22])=[O:21])[N:38]2[N:37]=1

Participants

Reactant 4

HCID 79001-Methoxy-2-propanol

HCID 81531Diisopropylethylamine

HCID 66711176HCID 66711176, compound

HCID 86661681Trifluoro-methanesulfonic acid 7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester

Product 1

HCID 66711981HCID 66711981, compound

Conditions

Temperature: 120 °C

Procedure

Into a 8-dram vial, (3-Amino-2-methoxy-phenyl)-(4-methyl-piperazin-1-yl)-methanone (107 mg, 0.430 mmol), Trifluoro-methanesulfonic acid 7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester (88.0 mg, 0.195 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-{2-[2-Methoxy-3-(4-methyl-piperazine-1-carbonyl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-N-methyl-methanesulfonamide a yellow solid (42 mg, 32%). LCMS (E/I+) 550.16 (M+H). NMR 1H (DMSO-d6)-9.79 (bs, 1H), 9.02 (s, 1H), 8.13 (bs, 1H), 8.06 (s, 1H), 7.90-7.96 (m, 1H), 7.45-7.65 (m, 3H), 7.09 (t, 1H, J=7.80 Hz), 7.05 (d, 1H, J=4.63 Hz), 7.00 (d, 1H, J=4.63 Hz), 6.92 (bs, 1H), 2.70-4.50 (m, 20H).

Workup

customThe solvent was removed under vacuum
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-fca80e24f8e1428f8e74be57051b9d0a
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08471005B2

Reaction notes

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