Sodium Carbonate → HCID 59511482, compound

HRID 1157790Notes

Reaction equation

HRID 1157790 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([O:32][CH3:33])=[C:6]2[C:10]([C:11](=[O:31])[C:12]([N:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:24]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=5)[N:23]=[N:22][N:21]=4)[CH2:16][CH2:15]3)=[O:13])=[CH:9][NH:8][C:7]=12.CC1(C)C(C)(C)OB([C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:53][CH2:52][N:51]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:50][CH2:49]3)=[CH:44][CH:43]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O.O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:33][O:32][C:5]1[CH:4]=[N:3][C:2]([C:42]2[CH:43]=[CH:44][C:45]([N:48]3[CH2:49][CH2:50][N:51]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:52][CH2:53]3)=[CH:46][CH:47]=2)=[C:7]2[NH:8][CH:9]=[C:10]([C:11](=[O:31])[C:12](=[O:13])[N:14]3[CH2:15][CH2:16][N:17]([C:20]4[N:24]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=5)[N:23]=[N:22][N:21]=4)[CH2:18][CH2:19]3)[C:6]=12

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27955144-(4-tert-Butoxycarbonylpiperazinyl)phenylboronic acid, pinacol esterHCID 59511493HCID 59511493, compound

Product 1

HCID 59511482HCID 59511482, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-(7-bromo-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (300 mg, 0.586 mmol), tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate (250 mg, 0.644 mmol), Na2CO3 (310 mg, 2.93 mmol) and PdCl2(dppf)2-CH2Cl2 adduct (47.8 mg, 0.059 mmol) in water (1.000 mL) and 1,4-dioxane (1 mL) was heated up at 80° C. for 2 h. The reaction mixture was cooled to room temperature, filtered through a silica gel pad and concentrated under reduced pressure. The resulting crude was purified by prep HPLC to give tert-butyl 4-(4-(4-methoxy-3-(2-oxo-2-(4-(1-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)phenyl)piperazine-1-carboxylate (250 mg, 62%) as white solid. LCMS: m/e 694.36 (M+H)+, ret time 1.68 min (method 8). 1H NMR (500 MHz, MeOD) δ ppm 1.52 (s, 9H) 3.41-3.46 (m, 4H) 3.47-3.51 (m, 2H) 3.52-3.56 (m, 2H) 3.64 (m, 4H) 3.69-3.75 (m, 2H) 3.86-3.95 (m, 2H) 4.17 (s, 3H) 7.28 (d, J=8.54 Hz, 2H) 7.63 (dd, J=7.63, 4.88 Hz, 1H) 7.77 (d, J=8.55 Hz, 2H) 7.90 (d, J=8.24 Hz, 1H) 8.00 (s, 1H) 8.17 (t, J=7.78 Hz, 1H) 8.68 (s, 2H)

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through a silica gel pad
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting crude was purified by prep HPLC

Sources & evidence

ORD record
ord-6f3704d766e64680927d219490964ce9
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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