Sodium Carbonate → 6-Chloro-19-pyridin-4-yl-14-oxa-2,4,8,23-tetraazatetracyclo[15.3.1.1(3,7).1(9,13)]tricosa-1(21),3(23),4,6,9(22),10,12,17,19-nonaene bis(trifluoroacetate)

HRID 541936Notes

Reaction equation

HRID 541936 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].Br[C:9]1[CH:10]=[C:11]2[CH:29]=[C:27]([CH:28]=1)[NH:26][C:25]1=[N:30][C:21](=[C:22]([Cl:31])[CH:23]=[N:24]1)[NH:20][C:19]1=[CH:32][C:15](=[CH:16][CH:17]=[CH:18]1)[O:14][CH2:13][CH2:12]2.[N:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:31][C:22]1[CH:23]=[N:24][C:25]2[NH:26][C:27]3[CH:28]=[C:9]([C:36]4[CH:37]=[CH:38][N:33]=[CH:34][CH:35]=4)[CH:10]=[C:11]([CH:29]=3)[CH2:12][CH2:13][O:14][C:15]3[CH:32]=[C:19]([NH:20][C:21]=1[N:30]=2)[CH:18]=[CH:17][CH:16]=3

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 6689746719-Bromo-6-chloro-14-oxa-2,4,8,23-tetraazatetracyclo[15.3.1.1(3,7).1(9,13)]tricosa-1(21),3(23),4,6,9(22),10,12,17,19-nonaene trifluoroacetate

Product 1

HCID 866362926-Chloro-19-pyridin-4-yl-14-oxa-2,4,8,23-tetraazatetracyclo[15.3.1.1(3,7).1(9,13)]tricosa-1(21),3(23),4,6,9(22),10,12,17,19-nonaene bis(trifluoroacetate)Yield 12.9%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 19-bromo-6-chloro-14-oxa-2,4,8,23-tetraazatetracyclo[15.3.1.1(3,7).1(9,13)]tricosa-1(21),3(23),4,6,9(22),10,12,17,19-nonaene trifluoroacetate (40 mg, 96 μmol), 4-pyridinylboronic acid (13 mg, 0.11 mmol), and 2 M sodium carbonate (0.14 mL, 0.29 mmol) in toluene (0.36 mL) and ethanol (0.36 mL) was degassed with nitrogen, treated with tetrakis(triphenylphosphine)palladium(O) (8 mg, 6.7 μmol), and heated at 85° C. for 12 h. The reaction mixture was concentrated and purified by preparative LCMS to give the desired product (4 mg, 7%) as a white solid. LCMS for C23H19ClN5O (M+H)+: m/z=416.0. 1H NMR (400 MHz, DMSO-d6): δ 9.62 (s, 1H), 9.20 (s, 1H), 8.90 (br s, 2H), 8.19 (s, 1H), 8.13-8.05 (m, 3H), 7.65 (s, 1H), 7.52 (s, 1H), 7.45 (s, 1H), 7.24 (dd, J=8.2, 8.0 Hz, 1H), 6.94-6.86 (m, 2H), 4.57-4.54 (m, 2H), 2.85-2.78 (m, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by preparative LCMS

Sources & evidence

ORD record
ord-a4068540d3f44d10815fbdd50ecdab1c
Source dataset
uspto-grants-2014_10
Patent number
US08871753B2

Reaction notes

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