Potassium Phosphate, Tribasic → 3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-6-(2-phenylcyclopropyl)pyrimidin-4(3H)-one

HRID 2059869노트

반응식

HRID 2059869 반응식
C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.Cl[C:21]1[N:26]=[CH:25][N:24]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]([OH:38])([CH3:37])[CH3:36])=[C:29]([O:39][CH3:40])[CH:28]=2)[C:23](=[O:41])[CH:22]=1.[C:42]1([CH:48]2[CH2:50][CH:49]2B(O)O)[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[OH:38][C:35]([CH3:37])([CH3:36])[CH2:34][O:33][C:30]1[CH:31]=[CH:32][C:27]([N:24]2[C:23](=[O:41])[CH:22]=[C:21]([CH:49]3[CH2:50][CH:48]3[C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[N:26]=[CH:25]2)=[CH:28][C:29]=1[O:39][CH3:40]

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 12982400(2-Phenylcyclopropyl)boronic acidHCID 585799166-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-pyrimidin-4(3H)-one

생성물 1

HCID 585798413-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-6-(2-phenylcyclopropyl)pyrimidin-4(3H)-one수율 23.49%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 1140Toluene용매

반응 조건

온도
100 °C

실험 절차

Tricyclohexyl phosphine (10 μL, 9.24 μmol) was added under nitrogen to a mixture of 6-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-pyrimidin-4(3H)-one Part A of Procedure 11 (10 mg, 0.031 mmol), 2-phenylcyclopropylboronic acid (5.5 mg, 0.034 mmol), palladium (II) acetate (2 mg, 6.16 μmol), and potassium phosphate, tribasic (20 mg, 0.09 mmol) in toluene (0.16 mL), and water (0.07 mL). The reaction stirred at 100° C. for 2 hours. The reaction mixture was filtered and concentrated to afford the crude product. The crude was purified using HPLC (C18 column/10:90:0.1 to 90:10:0.1 MeOH—H2O-TFA) to afford the desired product 3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-6-(2-phenylcyclopropyl)pyrimidin-4(3H)-one K-1 (3 mg, 7.23 μmol, 23.49% yield) as a light yellow solid. LC/MS 407 (M+H)+, tR 0.92 min (method 5); 1H NMR (400 MHz, CHLOROFORM-d) δ 8.11 (1H, s), 7.28-7.41 (2H, m), 7.20-7.26 (1H, m), 7.13-7.19 (2H, m), 7.00 (1H, d), 6.85-6.90 (2H, m), 6.48 (1H, s), 3.88 (5H, br. s.), 2.60-2.66 (1H, m), 2.08-2.14 (1H, m), 1.75-1.81 (1H, m), 1.51-1.57 (1H, m), 1.37 (6H, s).

후처리

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated
  3. customto afford the crude product
  4. customThe crude was purified

출처 및 근거

ORD 기록
ord-9caabd27b0534bec9ae6db7c91b9afa7
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08278316B2

반응 노트

불러오는 중…