Potassium Phosphate, Tribasic → 3-(3-(tert-butyldimethylsilyloxy)propyl)-5-(1-hydroxy-3-methylbutyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

HRID 60166

반응식

HRID 60166 반응식
[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:29])[CH2:25][CH:26]([CH3:28])[CH3:27])=[C:20](Cl)[N:21]=[CH:22][C:15]=2[N:14]([CH3:30])[C:13]1=[O:31])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH:32]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O)([CH3:34])[CH3:33].[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:29])[CH2:25][CH:26]([CH3:28])[CH3:27])=[C:20]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=3[CH:32]([CH3:34])[CH3:33])[N:21]=[CH:22][C:15]=2[N:14]([CH3:30])[C:13]1=[O:31])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

참가 물질

7

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 27734772-Isopropylbenzeneboronic acidHCID 1317370773-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione2회

생성물 1

HCID 1317370833-(3-(tert-butyldimethylsilyloxy)propyl)-5-(1-hydroxy-3-methylbutyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione수율 14.3%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

To a solution of 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (See Compound 48, step 1, 130 mg, 0.277 mmol), 2-isopropylphenyl boronic acid (90.8 mg, 0.554 mmol), aq. 2M K3PO4 (0.68 ml, 1.35 mmol) in dioxane (1 mL) and water (0.2 mL) was added Pd(dppf)Cl2 (8 mg, 0.01 mmol). The reaction was degassed with nitrogen (3×), heated at 120° C. (MW) for 1.5 h, cooled to RT, diluted with EA (10 mL) and water (2 mL) and filtered. The filtrate was concentrated to a residue which was purified by Prep TLC PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-5-(1-hydroxy-3-methylbutyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (22 mg, 14.3% yield) as a colorless oil. LCMS: MH+ 554 and TR=2.415 min.

후처리

  1. customThe reaction was degassed with nitrogen (3×)
  2. temperatureheated at 120° C. (MW) for 1.5 h
  3. additiondiluted with EA (10 mL) and water (2 mL)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated to a residue which
  6. customwas purified by Prep TLC PE/EA (2:1)

출처 및 근거

ORD 기록
ord-4ebb7317717d4a3da8784b95529c9ffa
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440973B2

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