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 1698015Notes

Reaction equation

HRID 1698015 reaction equation
[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

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 517044Potassium AcetateHCID 59239275Pyrido[3,4-d]pyriMidine-7(6H)-carboxylic acid, 2-chloro-5,8-dihydro-4-[(3S)-3-Methyl-4-Morpholinyl]-, 1,1-diMethylethyl esterHCID 671809445-Methyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-amine

Product 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

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Procedure

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)+

Workup

  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

Sources & evidence

ORD record
ord-598afd796ee146b29b98b5f9fdedb462
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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