Formaldehyde → N-{4-[4-amino-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N'-[2-fluoro-5-(trifluoromethyl)phenyl]urea

HRID 73701Notes

Reaction equation

HRID 73701 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH2:7]=O.[NH2:9][C:10]1[C:15]2=[C:16]([C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:29][C:30]4[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=4[F:40])=[O:28])=[CH:22][CH:21]=3)[C:17]([CH3:19])=[CH:18][N:14]2[N:13]=[CH:12][N:11]=1>C(O)(=O)C>[NH2:9][C:10]1[C:15]2=[C:16]([C:20]3[CH:21]=[CH:22][C:23]([NH:26][C:27]([NH:29][C:30]4[CH:35]=[C:34]([C:36]([F:37])([F:38])[F:39])[CH:33]=[CH:32][C:31]=4[F:40])=[O:28])=[CH:24][CH:25]=3)[C:17]([CH3:19])=[C:18]([CH2:7][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[N:14]2[N:13]=[CH:12][N:11]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 8083MorpholineHCID 57758309HCID 57758309, compound

Product 1

HCID 23653357N-{4-[4-amino-6-methyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N'-[2-fluoro-5-(trifluoromethyl)phenyl]ureaYield 17.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of morpholine (35 mg, 41 mmol) and 100 uL acetic acid were sonicated until homogeneous, then treated with 37% aqueous formaldehyde (30 uL, 33 mg, 41 mmol) and the mixture added to a solution of N-[4-(4-amino-6-methylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-N′-[2-fluoro-5-(trifluoromethyl)-phenyl]urea (150 mg, 34 mmol) in 1 mL acetic acid. This mixture was stirred for 16 h at 60° C. and then concentrated in vacuo. The residue was dissolved in methanol with 5 drops of trifluoroacetic acid and purified by RP-HPLC to provide the title compound as a white solid (32.3 mg, 17.1% yield). 1H-NMR (DMSO-d6) δ 9.34 (d, J=9.6 Hz, 1H), 8.94 (bs, 1H), 8.62 (d, J=7.2 Hz, 1H), 7.92 (s, 1H), 7.85 (s, 1H), 7.61 (d, J=8.7 Hz, 2H), 7.47 to 7.53 (m, m1H), 7.33 to 7.41 (m, 1H), 7.31 (d, J=8.7 Hz, 2H), 3.80 (s, 2H), 3.48 to 3.55 (m, 4H), 2.34 to 2.44 (m, 4H); MS [M+H]+=544.1; LCMS RT=2.70.

Workup

  1. customwere sonicated until homogeneous,
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in methanol with 5 drops of trifluoroacetic acid
  4. custompurified by RP-HPLC

Sources & evidence

ORD record
ord-1b9df1dd168c430880ceb333d4a6518a
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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