Potassium Phosphate, Tribasic → HCID 24874900, compound

HRID 2264710Notes

Reaction equation

HRID 2264710 reaction equation
C(OC([NH:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([C:26]2[CH:27]=[CH:28][C:29](OS([C:44]([F:47])([F:46])[F:45])(=O)=O)=[C:30]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=3)[CH:31]=2)([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[N:10]=1)=O)(C)(C)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COCC[O:60][CH3:61].O.C([OH:65])C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:47][C:44]([F:45])([F:46])[C:61]([OH:60])=[O:65].[CH3:39][O:38][C:34]1[CH:33]=[C:32]([C:30]2[CH:29]=[CH:28][CH:27]=[C:26]([C:11]3([C:18]4[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=4)[C:12]4[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=4)[C:9]([NH2:8])=[N:10]3)[CH:31]=2)[CH:37]=[CH:36][CH:35]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 59596278HCID 59596278, compoundHCID 86587095Dimethoxyethane ethanol water

Product 1

HCID 24874900HCID 24874900, compound

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst2×

Conditions

Temperature
125 °C

Procedure

To trifluoro-methanesulfonic acid 5-[3-tert-butoxycarbonylamino-1-(4-methoxy-phenyl)-1H-isoindol-1-yl]-3′-methoxy-biphenyl-2-yl ester (Scheme #2, G) (50 mg, 0.075 mmol) was added potassium phosphate (32 mg, 0.15 mmol), dichlorobis(triphenylphosphine)palladium(II) (16 mg, 0.022 mmol), and 1,2-dimethoxyethane: water:ethanol (7:3:2, 2.0 mL). The reaction was heated in a microwave at 125° C. for 15 minutes, more dichlorobis(triphenylphosphine)palladium(II) (16 mg, 0.022 mmol) was added, and the reaction reheated at 125° C. for 15 minutes. The solvent was removed under reduced pressure and the crude material dissolved in acetonitrile/water with trifluoroacetic acid (75:25:0.1, 1.0 mL), the insoluble material was filtered off and the filtrate was purified using RP-HPLC AG1 (tR=21.2 min). The combined purified fractions were lyophilized to give the title compound (9.0 mg). 1H NMR (300 MHz, DMSO-d6/TFA-d) δ 8.33 (d, J=7.7 Hz, 1 H) 7.87 (m, 2 H), 7.22-7.13 (m, 4 H), 7.76-7.64 (m, 2 H), 7.59-7.47 (m, 2 H), 7.40-7.29 (m, 2 H), 6.97 (d, J=8.8 Hz, 3 H), 3.81 (s, 3 H), 3.76 (s, 3 H); MS (ES+) m/z 421 [M+1]+; tR=2.08 min.

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe crude material dissolved in acetonitrile/water with trifluoroacetic acid (75:25:0.1, 1.0 mL)
  3. filtrationthe insoluble material was filtered off
  4. customthe filtrate was purified
  5. customThe combined purified fractions

Sources & evidence

ORD record
ord-9b615b937b4f4cc29c88979444bc9c4c
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

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