Diisopropylethylamine → [(R)-1-(2-{1-[(5-Chloro-2,4-dimethoxy-phenylcarbamoyl)-methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-acetyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester

HRID 472727Notes

Reaction equation

HRID 472727 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.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:56]([O:60][C:61](=[O:68])[NH:62][C@@H:63]1[CH2:67][CH2:66][NH:65][CH2:64]1)([CH3:59])([CH3:58])[CH3:57].CCN(C(C)C)C(C)C>O.CN(C=O)C>[C:56]([O:60][C:61](=[O:68])[NH:62][C@@H:63]1[CH2:67][CH2:66][N:65]([C:24](=[O:26])[CH2:23][N:14]2[C:15](=[O:22])[C:16]3[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:12]([CH2:11][C:9](=[O:10])[NH:8][C:6]3[CH:7]=[C:2]([Cl:1])[C:3]([O:30][CH3:31])=[CH:4][C:5]=3[O:28][CH3:29])[C:13]2=[O:27])[CH2:64]1)([CH3:59])([CH3:57])[CH3:58]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1514397(3R)-(+)-3-(tert-Butoxycarbonylamino)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 68591551[(R)-1-(2-{1-[(5-Chloro-2,4-dimethoxy-phenylcarbamoyl)-methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-acetyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

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 (50.9 mg, 0.11 mmol), HATU (49.4 mg, 0.12 mmol), and (R)-Pyrrolidin-3-yl-carbamic acid tert butyl ester (25.7 mg, 0.12 mmol), DMF (3 ml) is added. The stirring mixture is treated with DIPEA (33 μL, 0.275 mmol) and stirred at RT for 1 hour. Water is added to the mixture with stirring giving rise to a solid. This is filtered off and washed with water to afford the title compound, [M+H]+ 616

Workup

  1. additionis added
  2. stirringwith stirring
  3. customgiving rise to a solid
  4. filtrationThis is filtered off
  5. washwashed with water

Sources & evidence

ORD record
ord-6582fffdfb8c423f867b033f6fb89af3
Source dataset
uspto-grants-2014_01
Patent number
US08633211B2

Reaction notes

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