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

HRID 2059869ノート

反応式

HRID 2059869 の反応式
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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-9caabd27b0534bec9ae6db7c91b9afa7
出典データセット
uspto-grants-2012_10
特許番号
US08278316B2

反応ノート

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