Potassium Phosphate, Tribasic → HCID 58215781, compound

HRID 1661664Notes

Reaction equation

HRID 1661664 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][NH:9][S:10]([CH3:13])(=[O:12])=[O:11])[CH:5]=[N:6][CH:7]=1.[C:14]([N:21]1[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([Cl:30])[CH:28]=2)[CH:23]=[C:22]1B(O)O)([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[C:17]([O:16][C:14]([N:21]1[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([Cl:30])[CH:28]=2)[CH:23]=[C:22]1[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([CH2:8][NH:9][S:10]([CH3:13])(=[O:12])=[O:11])[CH:3]=1)=[O:15])([CH3:20])([CH3:18])[CH3:19]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 441191511-Boc-6-chloroindole-2-boronic acidHCID 59534656N-[(5-Bromo-3-pyridinyl)methyl]methanesulfonamide

Product 1

HCID 58215781HCID 58215781, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

A flask is charged with N-(5-bromo-pyridin-3-ylmethyl)-methanesulfonamide (Example 163a, 530 mg, 2 mmol), N-Boc-6-chloro-indole-2-boronic acid (525 mg, 3.0 mmol), s-Phos (41 mg, 0.10 mmol), finely crushed potassium phosphate (849 mg, 4.0 mmol) and toluene (20 mL), and the mixture is degassed for 15 min. Pd2dba3 (37 mg, 0.04 mmol) is added and the mixture is stirred at 85° C. for 1 h. The mixture is cooled to room temperature, diluted with DCM and silica gel (10 g) is added. The mixture is concentrated in vacuo and the residue is purified by silica gel flash chromatography eluting with a 0 to 90% ethyl acetate-heptane gradient to give 6-chloro-2-[5-(methanesulfonylamino-methyl)-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester. MS (ESI) m/z 436.1 and 437.9 (M+H)+.

Workup

  1. customthe mixture is degassed for 15 min
  2. temperatureThe mixture is cooled to room temperature
  3. additionis added
  4. concentrationThe mixture is concentrated in vacuo
  5. customthe residue is purified by silica gel flash chromatography
  6. washeluting with a 0 to 90% ethyl acetate-heptane gradient

Sources & evidence

ORD record
ord-99d478a4a07745b6a7f2634afb81995d
Source dataset
uspto-grants-2011_10
Patent number
US08030334B2

Reaction notes

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