Potassium Phosphate, Tribasic → [2-(2,6-Dichloro-4-cyano-phenyl)-thiazolo[5,4-c]pyridin-4-yl]-carbamic acid tert-butyl ester

HRID 2366238Notes

Reaction equation

HRID 2366238 reaction equation
Br[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:18]([Cl:19])=[CH:17][C:14]([C:15]#[N:16])=[CH:13][C:12]=3[Cl:20])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[C:21](=[O:28])([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH2:22].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.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]>[C:24]([O:23][C:21](=[O:28])[NH:22][C:2]1[C:7]2[S:8][C:9]([C:11]3[C:18]([Cl:19])=[CH:17][C:14]([C:15]#[N:16])=[CH:13][C:12]=3[Cl:20])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1)([CH3:27])([CH3:26])[CH3:25]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866689964-(4-Bromothiazolo[5,4-c]pyridin-2-yl)-3,5-dichlorobenzonitrile

Product 1

HCID 66801860[2-(2,6-Dichloro-4-cyano-phenyl)-thiazolo[5,4-c]pyridin-4-yl]-carbamic acid tert-butyl esterYield 76%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-(4-bromo-thiazolo[5,4-c]pyridin-2-yl)-3,5-dichloro-benzonitrile (0.578 g, 1.50 mmol), tert-butyl carbamate (1.76 g, 15.0 mmol), Pd2(dba)3 (0.069 g, 0.075 mmol), XantPhos (0.087 g, 0.15 mmol) and tribasic potassium phosphate (0.635 g, 3.0 mmol) in toluene (10 mL) and water (1.5 mL) was degassed with argon then heated at 80° C. for 3 hours. The reaction mixture was filtered through Celite® and washed with EtOAc. The filtrate was washed with water then brine, dried over Na2SO4 and concentrated under reduced pressure. The resultant residue was purified by silica gel flash chromatography (0-50% EtOAc in pentane) to give the desired compound as an off-white solid (0.48 g, 76% yield). 1H NMR (300 MHz, CDCl3): δ 8.35 (d, J=5.6 Hz, 1H), 7.79 (d, J=5.6 Hz, 1H), 7.75 (s, 2H), 1.56 (s, 9H).

Workup

  1. customwas degassed with argon
  2. filtrationThe reaction mixture was filtered through Celite®
  3. washwashed with EtOAc
  4. washThe filtrate was washed with water
  5. dry with materialbrine, dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe resultant residue was purified by silica gel flash chromatography (0-50% EtOAc in pentane)

Sources & evidence

ORD record
ord-ba70db36dca94a869b440f8832563f6d
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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