Aniline → HCID 71738929, compound

HRID 338692Notes

Reaction equation

HRID 338692 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](O)=[O:17])=[CH:14][CH:13]=3)[CH2:9][CH2:8][C:6]=2[N:7]=1.[NH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=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>CN(C=O)C.[OH-].[Na+]>[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:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:17])=[CH:14][CH:13]=3)[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 6115Aniline2×HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86695819HCID 86695819, compound

Product 1

HCID 71738929HCID 71738929, compoundYield 53.6%

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzoic acid (54 mg, 0.20 mmol), aniline (0.027 mL, 0.30 mmol), and N,N-diisopropylethylamine (0.174 mL, 1.0 mmol) in 1.5 mL DMF at room temperature was added HBTU (83 mg, 0.22 mmol). The reaction was stirred at room temperature for 1.5 hours, but also briefly warmed to approx. 60° C. three times during this time. At 2 hours additional 0.025 mL aniline was added and the reaction briefly warmed to approx. 60° C. three times. After 22 hours, the reaction was stored in the freezer for 3 days, then warmed to room temperature, 8 drops 1.0 M NaOH added, and the mixture stirred for 5 minutes. The reaction was partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The resulting solid was triturated with EtOAc to give the title compound as an off-white solid (37 mg, 53%). 1H NMR (DMSO-d6) δ: 9.92 (s, 1H), 8.13 (s, 1H), 7.86-7.92 (m, 2H), 7.73-7.78 (m, 2H), 7.28-7.35 (m, 2H), 7.02-7.10 (m, 3H), 6.43 (s, 2H), 4.36 (s, 2H), 3.71 (t, J=6.0 Hz, 2H), 2.75 (t, J=5.9 Hz, 2H).

Workup

  1. temperaturealso briefly warmed to approx. 60° C. three times during this time
  2. customthe reaction
  3. temperaturebriefly warmed to approx. 60° C. three times
  4. waitAfter 22 hours
  5. waitthe reaction was stored in the freezer for 3 days
  6. temperaturewarmed to room temperature
  7. stirringthe mixture stirred for 5 minutes
  8. customThe reaction was partitioned between EtOAc and aqueous Na2CO3 solution
  9. washthe EtOAc layer washed with H2O, brine
  10. dry with materialdried with anhydrous Na2SO4 and rotary evaporated
  11. customThe resulting solid was triturated with EtOAc

Sources & evidence

ORD record
ord-03ffc7b9e6cd4550950cb55cd8a53ba1
Source dataset
uspto-grants-2014_11
Patent number
US08889870B2

Reaction notes

Loading…