Sodium Carbonate → HCID 46896832, compound

HRID 2408151Notes

Reaction equation

HRID 2408151 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[CH3:7][C:8]1[CH:13]=[CH:12][C:11](B(O)O)=[CH:10][CH:9]=1.Br[C:18]1[CH:50]=[CH:49][C:21]([O:22][CH:23]([C:42]2[CH:47]=[CH:46][C:45]([Cl:48])=[CH:44][CH:43]=2)[C@@H:24]([C:28]2[CH:41]=[CH:40][C:31]([C:32]([NH:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:33])=[CH:30][CH:29]=2)[CH2:25][CH2:26][CH3:27])=[CH:20][C:19]=1[C:51]#[N:52]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:48][C:45]1[CH:44]=[CH:43][C:42]([C@H:23]([O:22][C:21]2[CH:49]=[CH:50][C:18]([C:11]3[CH:12]=[CH:13][C:8]([CH3:7])=[CH:9][CH:10]=3)=[C:19]([C:51]#[N:52])[CH:20]=2)[C@@H:24]([C:28]2[CH:29]=[CH:30][C:31]([C:32]([NH:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:33])=[CH:40][CH:41]=2)[CH2:25][CH2:26][CH3:27])=[CH:47][CH:46]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 79799Tolylboronic acidHCID 86660368HCID 86660368, compound

Product 1

HCID 46896832HCID 46896832, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a flask charged with Na2CO3 (2.0 M in water, 132 μL, 0.263 mmol), Pd(PPh3)4 (10.1 mg, 8.77 μmol) and (4-methylphenyl)boronic acid (36.5 mg, 0.175 mmol) was added a solution of the product from Step A (50 mg, 0.088 mmol) in DMF, then the mixture was stirred at 60° C. overnight. After cooling to RT, the mixture was purified by preparative reverse phase HPLC eluting with 50-100% acetonitrile/water+0.1% TFA to afford the title compound. 1H NMR (500 MHz, CD3OD): δ 7.81 (d, J=8.5 Hz, 2H); 7.43 (d, J=7.5 Hz, 4H); 7.36 (t, J=8.5 Hz, 4H); 7.35 (d, J=8.5 Hz, 1H); 7.28 (d, J=3.0 Hz, 1H); 7.26 (d, J=8.0 Hz, 2H); 7.19 (dd, J=8.5, 2.5 Hz, 1H); 5.77 (d, J=7.0 Hz, 1H); 3.65-3.61 (m, 2H); 3.31 (m, 1H), 3.25 (s, 3H); 2.65 (t, J=6.5 Hz, 2H); 1.88-1.86 (m, 1H); 1.63-1.61 (m, 1H); 1.16-1.11 (m, 2H); 0.79 (t, J=7.0 Hz, 3H); LC1 1.27 min. (M+H)+ 581.

Workup

  1. temperatureAfter cooling to RT
  2. customthe mixture was purified by preparative reverse phase HPLC
  3. washeluting with 50-100% acetonitrile/water+0.1% TFA

Sources & evidence

ORD record
ord-5127acf9bf7b4b19b221676d56691b13
Source dataset
uspto-grants-2014_08
Patent number
US08809579B2

Reaction notes

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