Tetrahydrofuran → HCID 11166599, compound

HRID 1243191Notes

Reaction equation

HRID 1243191 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[N:10]1[CH2:19][C:18]2[C:13](=[N:14][C:15]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[N:16][CH:17]=2)[N:12]([C@:28](O[SiH3])([CH3:46])[C:29](C2C=CC=CC=2)(C2C=CC=CC=2)C(C)(C)C)[C:11]1=[O:49].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[O:68]1CCCC1>>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[N:10]1[CH2:19][C:18]2[C:13](=[N:14][C:15]([NH:20][C:21]3[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=3)=[N:16][CH:17]=2)[N:12]([C@@H:28]([CH3:46])[CH2:29][OH:68])[C:11]1=[O:49]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 131725976HCID 131725976, compound

Product 1

HCID 11166599HCID 11166599, compound

Procedure

(S)-3-(2-Fluoro-4-methoxy-phenyl)-7-(4-fluoro-phenylamino)-1-(2-tert-butyl-diphenyl-silanyloxy-1-methyl-ethyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (0.33 g, 0.46 mmol) was dissolved in anhydrous tetrahydrofuran (3.5 mL) and treated with tetrabutylammonium fluoride (1.0 M in tetrahydrofuran, 1.90 mL, 1.90 mmol) (Aldrich). The reaction was stirred in a water bath that was maintained in the 25–35° C. range. The reaction was complete after 4 hours and was concentrated. The residue was redissolved in ethyl acetate and washed with water and brine. The organic phase was dried over anhydrous sodium sulfate and concentrated. Purification by flash chromatography (Biotage 40S, 75:25 ethyl acetate-hexanes) followed by crystallization from ethyl acetate-hexanes gave (S)-(+)-3-(2-fluoro-4-methoxy-phenyl)-7-(4-fluoro-phenylamino)-1-(2-hydroxy-1-methyl-ethyl)-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one as a white solid. (Yield 0.18 g, 83.5%). Melting Point: 173–177° C.

Workup

  1. temperaturewas maintained in the 25–35° C. range
  2. concentrationwas concentrated
  3. dissolutionThe residue was redissolved in ethyl acetate
  4. washwashed with water and brine
  5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customPurification by flash chromatography (Biotage 40S, 75:25 ethyl acetate-hexanes)
  8. customfollowed by crystallization from ethyl acetate-hexanes

Sources & evidence

ORD record
ord-9473f18ed34d4b5ca994e798ee20862b
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

Loading…