Potassium Phosphate, Tribasic → HCID 59375021, compound

HRID 661929Notes

Reaction equation

HRID 661929 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:12]([C:15]([NH2:17])=[O:16])=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH:7]([CH2:18][OH:19])[CH2:8][C:9]=1[NH:10]2.[CH3:20][C:21]1[C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][CH:24]=[CH:23][C:22]=1[N:36]1[CH2:44][C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:37]1=[O:45].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.CCOC(C)=O.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>[OH:19][CH2:18][CH:7]1[CH2:6][CH2:5][C:4]2[C:3]3[C:11](=[C:12]([C:15]([NH2:17])=[O:16])[CH:13]=[CH:14][C:2]=3[C:26]3[CH:25]=[CH:24][CH:23]=[C:22]([N:36]4[CH2:44][C:43]5[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=5)[C:37]4=[O:45])[C:21]=3[CH3:20])[NH:10][C:9]=2[CH2:8]1

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 666064602,3-Dihydro-2-[2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1H-isoindol-1-one2×HCID 66606546HCID 66606546, compound2×

Product 1

HCID 59375021HCID 59375021, compoundYield 58.9%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-bromo-2-(hydroxymethyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide (Intermediate 30-3(a), 80 mg, 0.248 mmol), 2-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)isoindolin-1-one (Intermediate 50-4, 130 mg, 0.371 mmol), 2 M aqueous tripotassium phosphate (0.371 mL, 0.743 mmol), and tetrakis(triphenylphosphine)palladium (14.30 mg, 0.012 mmol) in toluene (3 mL) and ethanol (1 mL) was sealed in a vial and heated at 100° C. for 6 hrs. The mixture was cooled and diluted with EtOAc, and the solution was washed with water, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from DCM to 96:3.6:0.4 DCM-methanol-28% aqueous ammonium hydroxide) to provide 2-(hydroxymethyl)-5-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide as a light yellow solid (68 mg, 53%). 1H NMR (400 MHz, chloroform-d) δ 7.79 (1H, d, J=7.91 Hz), 7.46-7.53 (1H, m), 7.38-7.44 (2H, m), 7.30 (1H, dd, J=7.91, 3.08 Hz), 7.14-7.26 (3H, m), 6.77 (1H, dd, J=7.69, 2.86 Hz), 4.59-4.74 (2H, m), 3.39-3.54 (3H, m), 2.72-2.80 (2H, m), 2.30-2.44 (2H, m), 1.80-2.10 (3H, m), 1.75 (3H, d, J=8.35 Hz). Mass spectrum m/z 466.1 (M+H)+.

Workup

  1. customwas sealed in a vial and
  2. temperatureThe mixture was cooled
  3. washthe solution was washed with water
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (
  7. washeluting with a gradient from DCM to 96:3.6:0.4 DCM-methanol-28% aqueous ammonium hydroxide)

Sources & evidence

ORD record
ord-f44bc0ea59bd440eba3f46ce7d8b8a00
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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