Diisopropylethylamine → N-(5-Chloro-2,4-dimethoxy-phenyl)-2-{3-[2-((S)-3-dimethylamino-pyrrolidin-1-yl)-2-oxo-ethyl]-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl}-acetamide

HRID 472726Notes

Reaction equation

HRID 472726 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](O)=[O:25])[C:13]2=[O:27])=[O:10])[CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:56][N:57]([CH3:63])[C@H:58]1[CH2:62][CH2:61][NH:60][CH2:59]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[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:60]3[CH2:61][CH2:62][C@H:58]([N:57]([CH3:63])[CH3:56])[CH2:59]3)=[O:25])[C:13]2=[O:27])[CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 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 59317687N-(5-Chloro-2,4-dimethoxy-phenyl)-2-{3-[2-((S)-3-dimethylamino-pyrrolidin-1-yl)-2-oxo-ethyl]-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl}-acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a vial charged with {1-[(5-chloro-2,4-dimethoxy-phenylcarbamoyl)-methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-acetic acid (50 mg, 0.11 mmol), HATU (46.6 mg, 0.12 mmol), and dimethyl-(S)-pyrrolidin-3-yl-amine (14.0 mg, 0.12 mmol) DCM (2 ml) is added. The mixture is treated with DIPEA (48.6 μL, 2.79 mmol) and stirred at RT for 1 hour. DCM (5 ml) is added to the mixture and washed with 1M HCl. The acidic aqueous phase is treated with 1M NaOH until the pH is adjusted to pH of 7-8. The product is extracted from the aqueous phase with EtOAc (3×10 ml). The organic portions are combined, washed with water (10 ml), dried (MgSO4), filtered and concentrated to afford the title compound, [M+H]+ 544

Workup

  1. additionis added
  2. washwashed with 1M HCl
  3. additionThe acidic aqueous phase is treated with 1M NaOH until the pH
  4. extractionThe product is extracted from the aqueous phase with EtOAc (3×10 ml)
  5. washwashed with water (10 ml)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-dd55b0b7886f4690a3815aceb5a02ca0
Source dataset
uspto-grants-2014_01
Patent number
US08633211B2

Reaction notes

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