N-[4-(4-amino-7-[3-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]propyl}pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-fluorophenyl]-N'-[2-fluoro-5-(trifluoromethyl)phenyl]urea → N-(4-{4-amino-7-[3-(1,4-oxazepan-4-yl)propyl]pyrrolo[2,1-f][1,2,4]triazin-5-yl}-2-fluorophenyl)-N'-[2-fluoro-5-(trifluoromethyl)phenyl]urea

HRID 1099286Notes

Reaction equation

HRID 1099286 reaction equation
NC1C2=C(C3C=CC(NC(NC4C=C(C(F)(F)F)C=CC=4F)=O)=C(F)C=3)C=C(CCCBr)N2N=CN=1.O1CCCNCC1.[NH2:44][C:45]1[C:50]2=[C:51]([C:65]3[CH:70]=[CH:69][C:68]([NH:71][C:72]([NH:74][C:75]4[CH:80]=[C:79]([C:81]([F:84])([F:83])[F:82])[CH:78]=[CH:77][C:76]=4[F:85])=[O:73])=[C:67]([F:86])[CH:66]=3)[CH:52]=[C:53]([CH2:54][CH2:55][CH2:56][N:57]3[CH2:61][CH2:60]C[C@H:58]3[CH2:62][O:63][CH3:64])[N:49]2[N:48]=[CH:47][N:46]=1>>[NH2:44][C:45]1[C:50]2=[C:51]([C:65]3[CH:70]=[CH:69][C:68]([NH:71][C:72]([NH:74][C:75]4[CH:80]=[C:79]([C:81]([F:83])([F:82])[F:84])[CH:78]=[CH:77][C:76]=4[F:85])=[O:73])=[C:67]([F:86])[CH:66]=3)[CH:52]=[C:53]([CH2:54][CH2:55][CH2:56][N:57]3[CH2:61][CH2:60][CH2:64][O:63][CH2:62][CH2:58]3)[N:49]2[N:48]=[CH:47][N:46]=1

Participants

4

Reactant 3

HCID 17751774N-[4-(4-amino-7-[3-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]propyl}pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-fluorophenyl]-N'-[2-fluoro-5-(trifluoromethyl)phenyl]ureaHCID 218732751,4-OxazepaneHCID 592319471-{4-[4-Amino-7-(3-bromopropyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea

Product 1

HCID 59232073N-(4-{4-amino-7-[3-(1,4-oxazepan-4-yl)propyl]pyrrolo[2,1-f][1,2,4]triazin-5-yl}-2-fluorophenyl)-N'-[2-fluoro-5-(trifluoromethyl)phenyl]ureaYield 22%

Procedure

1-{4-[4-amino-7-(3-bromopropyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-3-[2-fluoro -5-(trifluoromethyl)phenyl]urea (50 mg, 0.088 mmol) and 1,4-oxazepane (36 mg, 0.263 mmol) were allowed to react using the procedure to make N-[4-(4-amino-7-{3-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]propyl}pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-fluorophenyl]-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea. The product was purified by column chromatography using a 4 g MPLC column. The eluent was 0-10.0% (2N NH3 in MeOH)/CH2Cl2 to yield clean product (11 mg, 22%) 1H-NMR (DMSO-d6) δ 9.41 (s, 1H), 9.25 (s, 1H), 8.66 (m, 1H), 8.26 (t, J=8.7 Hz, 1H), 7.89 (s, 1H), 7.52 to 7.22 (m, 4H), 6.58 (s, 1H), 3.66 to 3.56 (m, 4H), 2.90 to 2.42 (m, 8H), 2.57 (m, 2H), 1.79 (m, 4H), MS [M+H]+=590.2; LCMS RT=2.61

Workup

  1. customto react
  2. customThe product was purified by column chromatography

Sources & evidence

ORD record
ord-e2d3ab4212674c6a898e9bf0142284df
Source dataset
uspto-grants-2012_03
Patent number
US08143393B2

Reaction notes

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