Aniline → HCID 21058688, compound

HRID 2216992Notes

Reaction equation

HRID 2216992 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 10054325HCID 10054325, compound

Product 1

HCID 21058688HCID 21058688, 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)-4-(S)-methyl-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (0.28 g; 0.45 mmol) (from Example 15a supra) and aniline (0.10 mL; 1.21 mmol) (Aldrich) in toluene (0.25 mL, dried over molecular sieves) was heated in an oil bath at 110° C. for 2 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-(S)-methyl-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one. (Yield 0.23 g; 73.0%). 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-5d3210b25f854c2e86c752af0e2876bc
Source dataset
uspto-grants-2006_09
Patent number
US07112676B2

Reaction notes

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