Diisopropylethylamine → 1-(4-methoxy-7-(pyrimidin-5-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione

HRID 1157777Notes

Reaction equation

HRID 1157777 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([C:9]2[CH:10]=[N:11][CH:12]=[N:13][CH:14]=2)=[C:5]2[NH:15][CH:16]=[C:17]([C:18](=[O:22])[C:19]([OH:21])=O)[C:4]=12.Cl.[C:24]1([N:30]2[C:34]([N:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)=[N:33][N:32]=[N:31]2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=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.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([C:9]2[CH:10]=[N:11][CH:12]=[N:13][CH:14]=2)=[C:5]2[NH:15][CH:16]=[C:17]([C:18](=[O:22])[C:19]([N:38]3[CH2:39][CH2:40][N:35]([C:34]4[N:30]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[N:31]=[N:32][N:33]=4)[CH2:36][CH2:37]3)=[O:21])[C:4]=12

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 428852091-(1-phenyl-1H-tetrazol-5-yl)piperazine hydrochlorideHCID 686909322-(4-methoxy-7-(pyrimidin-5-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid

Product 1

HCID 595114891-(4-methoxy-7-(pyrimidin-5-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dioneYield 13.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-(4-methoxy-7-(pyrimidin-5-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (50 mg, 0.168 mmol), 1-(1-phenyl-1H-tetrazol-5-yl)piperazine hydrochloride (40.2 mg, 0.151 mmol) and 2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (59.2 mg, 0.184 mmol) in DMF (1 ml) was added N,N-Diisopropylethylamine (0.146 ml, 0.838 mmol). The mixture was stirred at room temperature for 4 hours. The mixture was diluted with 150 ml of CH2Cl2 and washed with 5% NaHCO3 (30 ml), brine (30 ml). The organic layer was dried over Na2SO4 and concentrated to give a residue, which was purified by prep. HPLC to give 1-(4-methoxy-7-(pyrimidin-5-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (10 mg, 0.020 mmol, 11.68% yield) (light tan solid). LCMS: m/e 511.4 (M+H)+, ret time 1.25 min. 1H NMR (500 MHz, MeOD) δ ppm 9.30 (s, 1H) 9.17 (s, 2H) 8.38 (s, 1H) 8.16 (s, 1H) 7.58-7.65 (m, 5H) 4.09 (s, 3H) 3.80-3.83 (m, 2H) 3.57-3.60 (m, 2H) 3.38-3.42 (m, 2H) 3.31-3.33 (m, 2H).

Workup

  1. washwashed with 5% NaHCO3 (30 ml), brine (30 ml)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. customto give a residue, which
  5. customwas purified by prep

Sources & evidence

ORD record
ord-4c422421c7e54962b8df2ba921dc3a26
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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