3-(Trifluoromethyl)aniline → HCID 86695821, compound

HRID 1052005Notes

Reaction equation

HRID 1052005 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=3)[CH2:9][CH2:8][C:6]=2[N:7]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:54][C:55]([F:64])([F:63])[C:56]1[CH:57]=[C:58]([CH:60]=[CH:61][CH:62]=1)[NH2:59]>CN(C=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[CH:20]=[CH:19][C:15]([C:16]([NH:59][C:58]4[CH:60]=[CH:61][CH:62]=[C:56]([C:55]([F:54])([F:63])[F:64])[CH:57]=4)=[O:18])=[CH:14][CH:13]=3)[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

6

Reactant 4

HCID 73753-(Trifluoromethyl)anilineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86695819HCID 86695819, compound

Product 1

HCID 86695821HCID 86695821, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzoic acid (27 mg, 0.10 mmol), N,N-diisopropylethylamine (0.087 mL, 0.50 mmol), and HBTU (42 mg, 0.11 mmol) in 1.0 mL DMF was stirred at room temperature for 10 minutes. Then 3-(trifluoromethyl)aniline (0.025 mL, 0.20 mmol) was added and the reaction heated at 55° C. for 18 hours and then 90° C. for 2 hours. The reaction mixture was partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with dilute aqueous HCl, aqueous Na2CO3 solution, brine, dried with anhydrous Na2SO4 and rotary evaporated. The resulting solid was chromatographed eluting with CHCl3, then gradient 2% to 5% MeOH/CHCl3 to give the title compound as a brownish-tan solid (3 mg, 8%). 1H NMR (CDCl3) δ: 8.15 (s, 1H), 7.93 (s, 1H), 7.80-7.89 (m, 4H), 7.44-7.51 (m, 1H), 7.35-7.40 (m, 1H), 6.94-7.00 (m, 2H), 5.00 (br. s., 2H), 4.39 (s, 2H), 3.73 (t, J=6.0 Hz, 2H), 2.94 (t, J=6.0 Hz, 2H)

Workup

  1. temperaturethe reaction heated at 55° C. for 18 hours
  2. wait90° C. for 2 hours
  3. customThe reaction mixture was partitioned between EtOAc and aqueous Na2CO3 solution
  4. washthe EtOAc layer washed with dilute aqueous HCl, aqueous Na2CO3 solution, brine
  5. dry with materialdried with anhydrous Na2SO4 and rotary evaporated
  6. customThe resulting solid was chromatographed
  7. washeluting with CHCl3

Sources & evidence

ORD record
ord-d225f354088047179d66637979aa3e38
Source dataset
uspto-grants-2016_07
Patent number
US09388176B2

Reaction notes

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