Triethylamine → HCID 25164432, compound

HRID 472725Notes

Reaction equation

HRID 472725 reaction equation
[Cl:1][C:2]1[C:3]([O:30][CH3:31])=[CH:4][C:5]([O:28][CH3:29])=[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:7]=1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:63][N:64]1[CH2:69][CH2:68][NH:67][CH2:66][CH2:65]1>CN1C(=O)CCC1.CC#N>[Cl:1][C:2]1[C:3]([O:30][CH3:31])=[CH:4][C:5]([O:28][CH3:29])=[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:67]3[CH2:68][CH2:69][N:64]([CH3:63])[CH2:65][CH2:66]3)=[O:26])[C:13]2=[O:27])[CH:7]=1

Participants

7

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 24896589{1-[(5-Chloro-2,4-dimethoxy-phenylcarbamoyl)-methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-acetic acid

Product 1

HCID 25164432HCID 25164432, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of {1-[(5-Chloro-2,4-dimethoxy-phenylcarbamoyl)-methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-acetic acid (0.515 g, 1.14 mmol) in NMP (8 ml), triethylamine (0.166 ml, 1.26 mmol) is added followed by HATU (0.452 g, 1.26 mmol). The mixture is stirred at RT for 5 minutes and then treated with 1-methylpiperazine (140.3 μL, 1.26 mmol). After 5 minutes at RT the reaction mixture is partitioned between EtOAc (25 ml) and water (25 ml). The phases are separated and the aqueous phase is washed further with EtOAc (2×20 ml). The organic extracts are combined, washed with saturated NaHCO3 (40 ml), brine (40 ml), dried (MgSO4), filtered and concentrated to give a brown oil. The residue is taken up in MeCN (5 ml) and passed through a 10 g Varian pre packed silica cartridge, eluting with MeCN then EtOAc to remove the impurities. The product is eluted off the column with MeOH. The MeOH fractions are combined and concentrated in vacuo and dried to afford the title compound, [M+H]+ 530.

Workup

  1. customAfter 5 minutes at RT the reaction mixture is partitioned between EtOAc (25 ml) and water (25 ml)
  2. customThe phases are separated
  3. washthe aqueous phase is washed further with EtOAc (2×20 ml)
  4. washwashed with saturated NaHCO3 (40 ml), brine (40 ml)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a brown oil
  9. washeluting with MeCN
  10. customEtOAc to remove the impurities
  11. washThe product is eluted off the column with MeOH
  12. concentrationconcentrated in vacuo
  13. customdried

Sources & evidence

ORD record
ord-f350172cc77046af8bb71d8b3dbb726c
Source dataset
uspto-grants-2014_01
Patent number
US08633211B2

Reaction notes

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