4-Methylmorpholine → 4-amino-5-(4-amino-3-fluorophenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide

HRID 2197526Notes

Reaction equation

HRID 2197526 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:14]3[CH:19]=[CH:18][C:17]([NH2:20])=[C:16]([F:21])[CH:15]=3)[C:9]([C:11]([OH:13])=O)=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1.[F:22][C:23]([F:27])([F:26])[CH2:24][NH2:25].N1C2C=CC=C(O[P+](N(C)C)(N(C)C)N(C)C)C=2N=N1.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C>[NH2:1][C:2]1[C:7]2=[C:8]([C:14]3[CH:19]=[CH:18][C:17]([NH2:20])=[C:16]([F:21])[CH:15]=3)[C:9]([C:11]([NH:25][CH2:24][C:23]([F:27])([F:26])[F:22])=[O:13])=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9773Ethanamine, 2,2,2-trifluoro-HCID 59549193HCID 59549193, compoundHCID 178486078HCID 178486078, compound

Product 1

HCID 595491724-amino-5-(4-amino-3-fluorophenyl)-N-(2,2,2-trifluoroethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamideYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-amino-5-(4-amino-3-fluorophenyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (24.6 g, 85.6 mmol) was added to a mixture of 2,2,2-trifluoro-1-aminoethane (42.4 g, 428 mmol), benzotriazolyloxytris(dimethylamino)phosphonium PF6 (56.8 g, 128 mmol) and 4-methylmorpholine (43.3 g, 428 mmol) in DMF (500 mL). The reaction mixture was stirred at rt for 16 h. The resulting precipitate was isolated by filtration and then washed with acetone and diethyl ether to give the desired product (22 g, 70%); 1H NMR (300 MHz, DMSO-d6) δ 8.37 (dd, J=8.5, 8.5 Hz, 1H), 8.12 (s, 1H), 7.94 (s, 1H), 7.92-8.03 (br s, 1H), 7.89 (s, 1H), 6.99 (dd, J=12.2, 1.8 Hz, 1H), 6.85 (dd, J=12.2, 1.8 Hz, 1H), 6.74-6.6.82 (m, 1H), 5.35 (s, 2H), 5.13-3.22 (br s, 1H), 3.87-4.01 (m, 2H); ES-MS m/z 369.2 (MH)+; HPLC RT (Method B) 2.05 min.

Workup

  1. customThe resulting precipitate was isolated by filtration
  2. washwashed with acetone and diethyl ether

Sources & evidence

ORD record
ord-5de83a4b89f8431c95ae6420c32dfb2e
Source dataset
uspto-grants-2012_12
Patent number
US08338594B2

Reaction notes

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