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 1698015노트

반응식

HRID 1698015 반응식
[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

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매2회

실험 절차

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)+

후처리

  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

출처 및 근거

ORD 기록
ord-598afd796ee146b29b98b5f9fdedb462
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08163763B2

반응 노트

불러오는 중…