1-(3-Fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4] triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea, bis-hydrochloride salt → N-(4-(6-(3-(Dimethylamino)propoxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yloxy)-3-fluorophenyl)nicotinamide, dihydrochloride salt

HRID 2117113Notes

Reaction equation

HRID 2117113 reaction equation
[ClH:1].Cl.FC1C=C(NC(NC(=O)CC2C=CC(F)=CC=2)=S)C=CC=1OC1C2=C(C)C(O[CH2:21][CH2:22][N:23]3[CH2:28]CN(C)C[CH2:24]3)=CN2N=CN=1.Cl.[F:46][C:47]1[CH:48]=[C:49]([NH:73][C:74](=[O:86])[CH2:75][C:76]([NH:78][C:79]2C=CC(F)=[CH:81][CH:80]=2)=O)[CH:50]=[CH:51][C:52]=1[O:53][C:54]1[C:59]2=[C:60]([CH3:72])[C:61]([O:63][CH2:64]CN3CCOCC3)=[CH:62][N:58]2[N:57]=[CH:56][N:55]=1>>[ClH:1].[ClH:1].[CH3:24][N:23]([CH3:28])[CH2:22][CH2:21][CH2:64][O:63][C:61]1[C:60]([CH3:72])=[C:59]2[N:58]([CH:62]=1)[N:57]=[CH:56][N:55]=[C:54]2[O:53][C:52]1[CH:51]=[CH:50][C:49]([NH:73][C:74](=[O:86])[C:75]2[CH:81]=[CH:80][CH:79]=[N:78][CH:76]=2)=[CH:48][C:47]=1[F:46]

Participants

3

Reactant 2

HCID 1317262361-(3-Fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4] triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea, bis-hydrochloride salt2×HCID 131727132N1-(3-Fluoro-4-(5-methyl-6-(2-morpholinoethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide, hydrochloride salt

Product 1

HCID 131727134N-(4-(6-(3-(Dimethylamino)propoxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yloxy)-3-fluorophenyl)nicotinamide, dihydrochloride saltYield 11%

Procedure

4-(6-(3-(Dimethylamino)propoxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yloxy)-3-fluorobenzenamine (54 mg, 0.15 mmol, Compound B of Example 32) as converted to the title compound (8.7 mg, 11 %) in a manner similar to the preparation of Compound D of Example 36. 1H NMR (CD3OD) δ 9.47 (s, 1H), 9.20-9.19 (m, 1H), 9.08-9.07 (m, 1H), 8.30-8.27 (m, 1H), 7.97-7.93 (m, 1H), 7.82 (s, 1H), 7.72 (s, 1H), 7.64-7.61 (m, 1H), 7.43-7.39 (m, 1H), 4.26-4.11 (m, 2H), 3.43-3.39 (m, 2H), 2.98 (s, 6H), 2.46 (s, 3H), 2.34-2.30 (m, 2H); HRMS(ESI), 463.1894 (M−H)− calc, 463.1905 (M−H)− found.

Sources & evidence

ORD record
ord-ed74b609cbfa44b4a0da80220da654ad
Source dataset
uspto-grants-2008_10
Patent number
US07439246B2

Reaction notes

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