4-Methylmorpholine → 1-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(pyridin-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidin-7(8H)-yl)ethane-1,2-dione

HRID 885056Notes

Reaction equation

HRID 885056 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[CH2:17][CH2:16][NH:15][CH2:14][C:10]=2[N:11]=[CH:12][N:13]=1.[CH3:18][O:19][C:20]1[CH:25]=[N:24][C:23]([N:26]2[CH:30]=[N:29][C:28]([CH3:31])=[N:27]2)=[C:22]2[NH:32][CH:33]=[C:34]([C:35](=[O:39])[C:36](O)=[O:37])[C:21]=12.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[CH3:18][O:19][C:20]1[CH:25]=[N:24][C:23]([N:26]2[CH:30]=[N:29][C:28]([CH3:31])=[N:27]2)=[C:22]2[NH:32][CH:33]=[C:34]([C:35](=[O:39])[C:36]([N:15]3[CH2:16][CH2:17][C:9]4[C:8]([C:3]5[CH:4]=[CH:5][CH:6]=[CH:7][N:2]=5)=[N:13][CH:12]=[N:11][C:10]=4[CH2:14]3)=[O:37])[C:21]=12

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 596815922-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acidHCID 670725294-(Pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine hydrochloride

Product 1

HCID 445556641-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(pyridin-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidin-7(8H)-yl)ethane-1,2-dioneYield 49.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

Part E: To a solution of 4-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine hydrochloride (0.137 g, 0.55 mmol) in DMF (15 mL) at 25° C. was added sequentially 2-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (0.151 g, 0.50 mmol), N-methylmorpholine (0.220 mL, 2.00 mmol), and TBTU (0.177 g, 0.55 mmol), and the mixture was stirred at 25° C. for 18 h. The reaction mixture was concentrated under vacuum, and the residue dissolved in hot methanol. The solution was allowed to cool slowly to room temperature. The precipitate was recovered by filtration, washed with methanol, and dried under vacuum to provide 1-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(pyridin-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidin-7(8H)-yl)ethane-1,2-dione (0.122 g, 49%) as an off-white solid; HRMS: 496.1835 (M+H)+ [calc'd: 496.1840]; 1H NMR (500 MHz, DMSO-d6) δ 12.44 (br s, 1H), 9.24 (m, 1H), 9.17 (s, 2/3H), 9.08 (s, 1/3H), 8.77 (m, 1/3H), 8.67 (m, 2/3H), 8.34 (s, 2/3H), 8.26 (s, 1/3H), 8.12-8.00 (m, 2H), 7.87 (m, 1H), 7.58 (m, 1/3H), 7.53 (m, 2/3H), 4.92 (s, 4/3H), 4.72 (s, 2/3H), 3.93 (m, 1/3H), 3.91 (s, 1H), 3.85 (s, 2H), 3.70 (m, 2/3H), 3.32 (m, 1/3H), 3.18 (m, 2/3H), 2.50 (s, 2H), 2.49 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. dissolutionthe residue dissolved in hot methanol
  3. temperatureto cool slowly to room temperature
  4. filtrationThe precipitate was recovered by filtration
  5. washwashed with methanol
  6. customdried under vacuum

Sources & evidence

ORD record
ord-09716dc15a9e4722a50ca3added5354c
Source dataset
uspto-grants-2012_08
Patent number
US08242124B2

Reaction notes

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