Tetrahydrofuran → 4-amino-5-(4-nitrophenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide

HRID 2197520Notes

Reaction equation

HRID 2197520 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:14]3[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=3)[C:9]([C:11](O)=[O:12])=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1.Cl.[F:24][C:25]([F:29])([F:28])[CH2:26][NH2:27].C(N(CC)CC)C.C1COCC1>S(Cl)(Cl)=O>[NH2:1][C:2]1[C:7]2=[C:8]([C:14]3[CH:15]=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=3)[C:9]([C:11]([NH:27][CH2:26][C:25]([F:29])([F:28])[F:24])=[O:12])=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 97722,2,2-Trifluoroethylamine hydrochlorideHCID 577579424-Amino-5-(4-nitrophenyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid

Product 1

HCID 577582594-amino-5-(4-nitrophenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamideYield 74.5%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

A solution 4-amino-5-(4-nitrophenyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (495 mg, 1.73 mmol) in thionyl chloride (15 mL) was heated (50° C.) for 3 h. Upon cooling to rt the reaction mixture was concentrated to dryness. The resulting acid chloride intermediate was combined with 2,2,2-trifluoro-ethylamine hydrochloride salt (587 mg, 4.33 mmol), triethylamine (1.15 ml, 8.66 mmol), and THF (8 mL). The reaction was stirred for 16 h and then concentrated in vacuo. The residue was dissolved in ethyl acetate (50 mL) and then washed with water. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was tritureated with ethyl acetate and methanol to afford the desired product (490 mg, 74%). 1H-NMR (300 MHz, DMSO-d6) 8.77 (t, J=6.2 Hz, 1H), 8.29 (s, 1H), 8.23 (d, J=8.9 Hz, 2H), 7.97 (s, 1. H), 7.59 (d, J=8.9 Hz, 2H), 3.91-3.99 (m, 2H); ES-MS m/z 381.1 (MH)+; HPLC RT (Method B) 2.33 min.

Workup

  1. concentrationwas concentrated to dryness
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  4. washwashed with water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b229767f6ea147699d197eccf60811ee
Source dataset
uspto-grants-2012_12
Patent number
US08338594B2

Reaction notes

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