Acetonitrile → (S)-tert-butyl 2-(4-(2-amino-5-methyl-1H-imidazol-1-yl)phenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate

HRID 1698015ノート

反応式

HRID 1698015 の反応式
[CH3:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][CH:8]=2)[C:5]([NH2:22])=[N:4][CH:3]=1.C([O-])(=O)C.[K+].Cl[C:29]1[N:30]=[C:31]([N:46]2[CH2:51][CH2:50][O:49][CH2:48][C@@H:47]2[CH3:52])[C:32]2[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][C:33]=2[N:34]=1.C(#N)C>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:22][C:5]1[N:6]([C:7]2[CH:8]=[CH:9][C:10]([C:29]3[N:30]=[C:31]([N:46]4[CH2:51][CH2:50][O:49][CH2:48][C@@H:47]4[CH3:52])[C:32]4[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][C:33]=4[N:34]=3)=[CH:11][CH:12]=2)[C:2]([CH3:1])=[CH:3][N:4]=1

参加物

7

反応物 4

HCID 6342AcetonitrileHCID 517044Potassium AcetateHCID 59239275(S)-tert-butyl 2-chloro-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylateHCID 671809445-Methyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-amine

生成物 1

HCID 59239461(S)-tert-butyl 2-(4-(2-amino-5-methyl-1H-imidazol-1-yl)phenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回

実験手順

Step 3—Synthesis of compound wh: 5-Methyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-amine (0.164 g, 0.000548 mol), Tetrakis(triphenylphosphine)palladium(0) (0.0931 g, 0.0000806 mol) Sodium carbonate (0.0887 g, 0.000837 mol) and Potassium acetate (0.1061 g, 0.001081 mol) were combined, nitrogen purged three times, added (S)-tert-butyl 2-chloro-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (0.219 g, 0.000594 mol) in dry Acetonitrile (4.60 mL, 0.0881 mol) and deoxygenated Water (2.80 mL, 0.155 mol) and the reaction was microwaved on 200 watts, 120° C. for 30 minutes on a CEM microwave. The reaction mixture was cooled to room temperature, diluted with water, extracted three times with 10% MeOH in dichloromethane, dried over Magnesium sulfate, filtered, concentrated, chromatographed through silica gel (120 g, 0-5% MeOH in dichloromethane), and purified by HPLC. 1H NMR (400 MHz, DMSO) δ 8.38 (t, J=8.8, 2H), 7.53 (d, J=8.7, 2H), 6.62 (d, J=1.0, 1H), 5.41 (s, 2H), 4.52 (t, J=15.6, 2H), 4.16 (d, J=6.7, 1H), 3.89 (d, J=10.8, 1H), 3.72-3.57 (m, 5H), 3.45 (dd, J=17.3, 7.1, 2H), 2.68 (d, J=6.6, 2H), 1.99 (d, J=0.9, 3H), 1.45 (d, J=7.9, 9H), 1.27 (d, J=6.6, 3H). LC/MS-m/z+506.3 (M+H)+

後処理

  1. customnitrogen purged three times
  2. customthe reaction was microwaved on 200 watts, 120° C. for 30 minutes on a CEM microwave
  3. extractionextracted three times with 10% MeOH in dichloromethane
  4. dry with materialdried over Magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed through silica gel (120 g, 0-5% MeOH in dichloromethane)
  8. custompurified by HPLC

出典と根拠

ORDレコード
ord-598afd796ee146b29b98b5f9fdedb462
出典データセット
uspto-grants-2012_04
特許番号
US08163763B2

反応ノート

読み込み中…