Diisopropylethylamine → 1-(7-(3-(hydroxymethyl)-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 885064Notes

Reaction equation

HRID 885064 reaction equation
[OH:1][CH2:2][C:3]1[N:7]=[CH:6][N:5]([C:8]2[N:9]=[CH:10][C:11]([O:22][CH3:23])=[C:12]3[C:16]([C:17](=[O:21])[C:18]([OH:20])=O)=[CH:15][NH:14][C:13]=23)[N:4]=1.[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]1[C:31]2[CH2:39][CH2:38][NH:37][CH2:36][C:32]=2[N:33]=[CH:34][N:35]=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][CH2:2][C:3]1[N:7]=[CH:6][N:5]([C:8]2[N:9]=[CH:10][C:11]([O:22][CH3:23])=[C:12]3[C:16]([C:17](=[O:21])[C:18]([N:37]4[CH2:38][CH2:39][C:31]5[C:30]([C:25]6[CH:26]=[CH:27][CH:28]=[CH:29][N:24]=6)=[N:35][CH:34]=[N:33][C:32]=5[CH2:36]4)=[O:20])=[CH:15][NH:14][C:13]=23)[N:4]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 580260572-(7-(3-(hydroxymethyl)-1H-1,2,4-triazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acidHCID 580260644-(Pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine

Product 1

HCID 446028601-(7-(3-(hydroxymethyl)-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 22.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(7-(3-(hydroxymethyl)-1H-1,2,4-triazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (23 mg, 0.072 mmol), 4-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine (15.39 mg, 0.072 mmol) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (27.9 mg, 0.087 mmol) in DMF (1 mL) was added N,N-diisopropylethylamine (0.127 mL, 0.725 mmol). The mixture was stirred at room temperature for 2 hours, diluted with MeOH and purified by prep. HPLC to give 1-(7-(3-(hydroxymethyl)-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 (9 mg, 0.016 mmol, 22% yield). LCMS: m/z 512.2 (M+H)+, 1.34 min (method 8). 1H NMR (500 MHz, DMSO-d6) d ppm 12.39-12.48 (m, 1H) 9.30-9.33 (m, 1H) 9.06-9.16 (m, 1H) 8.64-8.76 (m, 1H) 8.29-8.39 (m, 1H) 7.98-8.10 (m, 2H) 7.87 (s, 1H) 7.49-7.58 (m, 1H) 4.70-4.92 (m, 2H) 4.65-4.67 (m, 2H) 3.83-3.90 (m, 3H) 3.68 (t, J=5.80 Hz, 2H) 3.16 (t, J=5.65 Hz, 2H).

Workup

  1. custompurified by prep

Sources & evidence

ORD record
ord-340b16fbf52b4d23aa2199fe6924e477
Source dataset
uspto-grants-2012_08
Patent number
US08242124B2

Reaction notes

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