Aniline → HCID 21058687, compound

HRID 2216991Notes

Reaction equation

HRID 2216991 reaction equation
[C:1]([Si:5]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[O:6][CH2:7][C@H:8]([N:10]1[C:15]2=[N:16][C:17](Cl)=[N:18][CH:19]=[C:14]2[C@@H:13]([CH3:21])[N:12]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[C:11]1=[O:30])[CH3:9])([CH3:4])([CH3:3])[CH3:2].[NH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:1]([Si:5]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[O:6][CH2:7][C@H:8]([N:10]1[C:15]2=[N:16][C:17]([NH:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[N:18][CH:19]=[C:14]2[C@@H:13]([CH3:21])[N:12]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[C:11]1=[O:30])[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 6115AnilineHCID 11758297HCID 11758297, compound

Product 1

HCID 21058687HCID 21058687, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1-[2-(tert-butyl-diphenyl-silanyloxy)-1-(R)-methyl-ethyl]-7-chloro-3-(4-methoxy-phenyl)-(R)-4-methyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (0.32 g; 0.51 mmol) (from Example 14e supra) and aniline (0.12 mL; 1.32 mmol) (Aldrich) in toluene (0.25 mL, dried over molecular sieves) was heated in an oil bath at 110° C. for 1.75 hours. The reaction was diluted with ethyl acetate and washed with water and brine, dried over anhydrous sodium sulfate and concentrated. The crude material was purified by flash chromatography (Biotage 40L; 40:60 ethyl acetate-hexanes) to give 1-[2-(tert-butyl-diphenyl-silanyloxy)-1-(R)-methyl-ethyl]-3-(4-methoxy-phenyl)-4-(R)-methyl-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one. (Yield 0.30 g; 81.6%). This material showed an e.e. of ≧95%.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customThe crude material was purified by flash chromatography (Biotage 40L; 40:60 ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-6737f9dc82a04c4e89e5a59de968d9c8
Source dataset
uspto-grants-2006_09
Patent number
US07112676B2

Reaction notes

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