Formaldehyde → HCID 57955256, compound

HRID 1094887Notes

Reaction equation

HRID 1094887 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:27]3[CH:32]=[CH:31][C:30]([NH:33][C:34]([NH:36][C:37]4[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[N:38]=4)=[O:35])=[CH:29][CH:28]=3)[C:17]([C:19]([NH:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[O:20])=[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:27]3[CH:32]=[CH:31][C:30]([NH:33][C:34]([NH:36][C:37]4[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[N:38]=4)=[O:35])=[CH:29][CH:28]=3)[C:17]([C:19]([NH:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[O:20])=[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 57758344HCID 57758344, compound

Product 1

HCID 57955256HCID 57955256, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

To a solution of morpholine (80.9 mg, 0.93 mmol) in acetic acid (1 mL) was added a 37% aqueous formaldehyde solution (0.07 mL, 0.93 mmol). The mixture was stirred at rt under nitrogen for 20 min and was added to a solution of Intermediate AP (4-amino-N-(2,2,2-trifluoroethyl)-5-{4-[({[6-(trifluoromethyl)pyridin-2-yl]amino}-carbonyl)-amino]phenyl}pyrrolo[2,1-f][1,2,4]triazin-6-carboxamide (50.0 mg, 0.093 mmol)) in acetic acid (2 mL). The resultant solution was heated (60° C.) overnight and concentrated. The crude material was directly purified by HPLC using a gradient of 35-40% MeCN in water containing 0.1% trifluoroacetic acid. The combined fractions were concentrated under reduced pressure. The residue was dissolved in EtOAc (15 mL). The organic layer was washed with a 2.0 M Na2CO3 aqueous solution (15 mL), brine (15 mL), dried (Na2SO4) and concentrated under reduced pressure to yield 18.7 mg (32%) of the title compound. 1H-NMR (DMSO-d6) 10.0 (t, J=6.3 Hz, 1H), 9.89 (bs, 1H), 9.71 (bs, 1H), 8.05-8.00 (m, 2H), 7.98 (s, 1H), 7.52-7.49 (m, 3H), 7.31 (d, J=8.6 Hz, 2H), 4.12-3.98 (m, 4H), 3.56 (bs, 4H), 2.44 ((bs, 4H); MS [M+H]+=638.1; LCMS RT=2.92 min.

Workup

  1. concentrationconcentrated
  2. customThe crude material was directly purified by HPLC
  3. concentrationThe combined fractions were concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in EtOAc (15 mL)
  5. washThe organic layer was washed with a 2.0 M Na2CO3 aqueous solution (15 mL), brine (15 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9ea5ab91e69840a2837d1d970e911ad7
Source dataset
uspto-grants-2012_03
Patent number
US08133995B2

Reaction notes

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