Diisopropylethylamine → 1-(7-(3-(1-hydroxyethyl)-1H-1,2,4-triazol-1-yl)-4-methoxy-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 885068Notes

Reaction equation

HRID 885068 reaction equation
[OH:1][CH:2]([C:4]1[N:8]=[CH:7][N:6]([C:9]2[N:10]=[CH:11][C:12]([O:23][CH3:24])=[C:13]3[C:17]([C:18](=[O:22])[C:19]([OH:21])=O)=[CH:16][NH:15][C:14]=23)[N:5]=1)[CH3:3].[N:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]1[C:32]2[CH2:40][CH2:39][NH:38][CH2:37][C:33]=2[N:34]=[CH:35][N:36]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C.CO>[OH:1][CH:2]([C:4]1[N:8]=[CH:7][N:6]([C:9]2[N:10]=[CH:11][C:12]([O:23][CH3:24])=[C:13]3[C:17]([C:18](=[O:22])[C:19]([N:38]4[CH2:39][CH2:40][C:32]5[C:31]([C:26]6[CH:27]=[CH:28][CH:29]=[CH:30][N:25]=6)=[N:36][CH:35]=[N:34][C:33]=5[CH2:37]4)=[O:21])=[CH:16][NH:15][C:14]=23)[N:5]=1)[CH3:3]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 580260644-(Pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidineHCID 580260672-(7-(3-(1-hydroxyethyl)-1H-1,2,4-triazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid

Product 1

HCID 446028611-(7-(3-(1-hydroxyethyl)-1H-1,2,4-triazol-1-yl)-4-methoxy-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 55.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(7-(3-(1-hydroxyethyl)-1H-1,2,4-triazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (18 mg, 0.054 mmol), 4-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine (1.53 mg, 0.054 mmol) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (20.93 mg, 0.065 mmol) in DMF (1 mL) was added N,N-diisopropylethylamine (0.095 mL, 0.543 mmol). The mixture was stirred at room temperature for 2 hours, diluted with MeOH and purified by prep. HPLC to give 1-(7-(3-(1-hydroxyethyl)-1H-1,2,4-triazol-1-yl)-4-methoxy-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 (17 mg, 0.030 mmol, 54.8% yield). LCMS: m/z 526.2 (M+H)+, 1.54 min (method 8). 1H NMR (500 MHz, MeOD) d ppm 9.17 (s, 1H) 8.99-9.10 (m, 1H) 8.61-8.74 (m, 1H) 8.27-8.32 (m, 1H) 7.92-8.04 (m, 2H) 7.74-7.79 (m, 1H) 7.43-7.53 (m, 1H) 5.09 (q, J=6.41 Hz, 1H) 4.80-5.02 (m, 2H) 3.76-4.02 (m, 5H) 3.24-3.38 (m, 2H) 1.60-1.89 (m, 3H).

Workup

  1. custompurified by prep

Sources & evidence

ORD record
ord-4937ffca8a874ade9973e6fa770499e3
Source dataset
uspto-grants-2012_08
Patent number
US08242124B2

Reaction notes

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