Triethylamine → HCID 59317685, compound

HRID 472734Notes

Reaction equation

HRID 472734 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]([CH2:11][N:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[N:14]([CH2:23][C:24]([OH:26])=O)[C:13]2=[O:27])=[O:10])[CH:5]=[C:4]([Cl:28])[N:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[CH3:60][N:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1>CN1C(=O)CCC1>[Cl:28][C:4]1[CH:5]=[C:6]([NH:8][C:9](=[O:10])[CH2:11][N:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[N:14]([CH2:23][C:24]([N:64]3[CH2:65][CH2:66][N:61]([CH3:60])[CH2:62][CH2:63]3)=[O:26])[C:13]2=[O:27])[CH:7]=[C:2]([Cl:1])[N:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59317679HCID 59317679, compound

Product 1

HCID 59317685HCID 59317685, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of {1-[(2,6-dichloro-pyridin-4-ylcarbamoyl)-methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-acetic acid (13.5 mg, 0.0318 mmol) in dry NMP (1.5 ml), HATU (13.3 mg, 0.035 mmol) is added followed by triethylamine (4.89 μL, 0.035 mmol). The orange solution is stirred at RT for 10 minutes, then treated with 1-methyl piperazine (3.89 μL, 0.035 mmol). The reaction mixture is stirred at RT and monitored by HPLC/LCMS until the starting material is consumed. The reaction mixture is partitioned between EtOAc (5 ml) and water (5 ml). The organic layer is separated and washed with brine (5 ml), dried (MgSO4), filtered and concentrated in vacuo. The crude product is purified by passing down a 5 g Isolute™ SCX2 (solid-supported sulfonic acid resin) cartridge, eluting with DCM (20 ml), MeOH (20 ml), and 7N NH3 in MeOH. The basic ammonia wash is concentrated in vacuo to afford the title compound as a white solid, [M+H]+ 505.

Workup

  1. stirringThe reaction mixture is stirred at RT
  2. customis consumed
  3. customThe reaction mixture is partitioned between EtOAc (5 ml) and water (5 ml)
  4. customThe organic layer is separated
  5. washwashed with brine (5 ml)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product is purified
  10. washeluting with DCM (20 ml), MeOH (20 ml), and 7N NH3 in MeOH
  11. washThe basic ammonia wash
  12. concentrationis concentrated in vacuo

Sources & evidence

ORD record
ord-7ae3b80cabc4412d873bc370f2182b10
Source dataset
uspto-grants-2014_01
Patent number
US08633211B2

Reaction notes

Loading…