Formaldehyde → HCID 57955163, compound

HRID 73698Notes

Reaction equation

HRID 73698 reaction equation
[CH2:1]=O.[CH3:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.[NH2:10][C:11]1[C:16]2=[C:17]([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33]([NH:35][C:36]4[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[CH:38][N:37]=4)=[O:34])=[CH:28][CH:27]=3)[C:18]([C:20]([N:22]([O:24][CH3:25])[CH3:23])=[O:21])=[CH:19][N:15]2[N:14]=[CH:13][N:12]=1>CC(O)=O>[NH2:10][C:11]1[C:16]2=[C:17]([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33]([NH:35][C:36]4[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[CH:38][N:37]=4)=[O:34])=[CH:28][CH:27]=3)[C:18]([C:20]([N:22]([O:24][CH3:25])[CH3:23])=[O:21])=[C:19]([CH2:3][N:4]3[CH2:9][CH2:8][N:7]([CH3:1])[CH2:6][CH2:5]3)[N:15]2[N:14]=[CH:13][N:12]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 531671-MethylpiperazineHCID 57955349HCID 57955349, compound

Product 1

HCID 57955163HCID 57955163, compoundYield 54.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

A solution of formaldehyde (0.22 mL, 3.0 mmol, 37% in H2O) and 1-methylpiperazine (0.33 mL, 3.0 mmol) in AcOH (0.5 mL) was added to a stirring solution of 4-amino-N-methoxy-N-methyl-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}-carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide (150 mg, 0.30 mmol) in AcOH (1.5 mL) at 80° C. The reaction was allowed to stir overnight until all starting material had been consumed as shown by HPLC (15 hrs). The reaction mixture was worked up by diluting with EtOAc and washing 1× with saturated sodium carbonate solution, 1× with saturated sodium bicarbonate solution, and 1× with brine. The organic layer was dried over Na2SO4 and concentrated to a brown powder. The crude product was purified by HPLC (10-70% ACN/H2O) to yield 100 mg (0.16 mmol, 54.5%) of the title compound. 1H-NMR (DMSO-d6). δ 10.02 (s, 1H), 9.89 (s, 1H), 8.59 (d, J=5.4 Hz, 1H), 8.14 (s, 1H), 8.06 (s, 1H), 7.67 (d, J=8.4 Hz, 2H), 7.42-7.37 (m, 3H), 3.87 (s, 2H), 2.51-2.38 (m, 4H), 2.35-2.20 (m, 4H), 2.14 (s, 3H). MS [M+H]+=613; LCMS RT=2.37 min.

Workup

  1. customhad been consumed
  2. customas shown by HPLC (15 hrs)
  3. additionby diluting with EtOAc
  4. washwashing 1× with saturated sodium carbonate solution, 1× with saturated sodium bicarbonate solution, and 1× with brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated to a brown powder
  7. customThe crude product was purified by HPLC (10-70% ACN/H2O)

Sources & evidence

ORD record
ord-31587f44e9ed48f1bb84429273d46120
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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