Potassium Phosphate, Tribasic → 3-(3-(tert-butyldimethylsilyloxy)propyl)-5-(hydroxy(phenyl)methyl)-1-methyl-6-(3-(trifluoromethoxy)phenyl)pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

HRID 60176

反応式

HRID 60176 の反応式
[Si:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[C:19]([CH:24]([OH:31])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:20](Cl)[N:21]=[CH:22][C:15]=2[N:14]([CH3:32])[C:13]1=[O:33])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:34][C:35]([F:47])([F:46])[O:36][C:37]1[CH:38]=[C:39](B(O)O)[CH:40]=[CH:41][CH:42]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[C:19]([CH:24]([OH:31])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:20]([C:39]3[CH:40]=[CH:41][CH:42]=[C:37]([O:36][C:35]([F:34])([F:46])[F:47])[CH:38]=3)[N:21]=[CH:22][C:15]=2[N:14]([CH3:32])[C:13]1=[O:33])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

参加物

7

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 1317370873-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(hydroxy(phenyl)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H, 3H)-dione

生成物 1

HCID 1317370883-(3-(tert-butyldimethylsilyloxy)propyl)-5-(hydroxy(phenyl)methyl)-1-methyl-6-(3-(trifluoromethoxy)phenyl)pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione収率 44%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a solution of 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(hydroxy(phenyl)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (400 mg, 0.817 mmol), 3-(trifluoromethoxy)phenylboronic acid (336.9 mg, 1.635 mmol), aq. 2M K3PO4 (2 ml, 4.085 mmol) in dioxane (10 mL) and water (2 mL) was added Pd(dppf)Cl2 (21 mg, 0.0288 mmol). The reaction was degassed with nitrogen (3×), heated at 120° C. (MW) for 2 h, cooled to RT, diluted with EA (20 mL) and water (8 mL) and filtered through Celite. The filtrate was concentrated to a residue which was purified by Prep TLC eluted with PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-5-(hydroxyl(phenyl)methyl)-1-methyl-6-(3-(trifluoromethoxy)phenyl)pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (220 mg, 44% yield) as colorless oil. LCMS: MH+ 616 and TR=2.334 min.

後処理

  1. customThe reaction was degassed with nitrogen (3×)
  2. temperatureheated at 120° C. (MW) for 2 h
  3. additiondiluted with EA (20 mL) and water (8 mL)
  4. filtrationfiltered through Celite
  5. concentrationThe filtrate was concentrated to a residue which
  6. customwas purified by Prep TLC
  7. washeluted with PE/EA (2:1)

出典と根拠

ORDレコード
ord-7be2c8ed69274e659bd5f1856f91b0c0
出典データセット
uspto-grants-2016_09
特許番号
US09440973B2

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