Potassium Phosphate, Tribasic → [3,5-Dichloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-phenyl]-carbamic acid tert-butyl ester

HRID 2366246Notes

Reaction equation

HRID 2366246 reaction equation
[Cl:1][C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([Cl:17])=[CH:15][C:14](I)=[CH:13][C:12]=3[Cl:19])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[C:20]([O:24][C:25](=[O:27])[NH2:26])([CH3:23])([CH3:22])[CH3:21].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.[O-]P([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:20]([O:24][C:25](=[O:27])[NH:26][C:14]1[CH:15]=[C:16]([Cl:17])[C:11]([C:9]2[S:8][C:7]3[C:2]([Cl:1])=[N:3][CH:4]=[CH:5][C:6]=3[N:10]=2)=[C:12]([Cl:19])[CH:13]=1)([CH3:23])([CH3:22])[CH3:21]

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 866689974-Chloro-2-(2,6-dichloro-4-iodophenyl)thiazolo[5,4-c]pyridine

Product 1

HCID 86669003[3,5-Dichloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-phenyl]-carbamic acid tert-butyl esterYield 90.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 4-chloro-2-(2,6-dichloro-4-iodophenyl)thiazolo[5,4-c]pyridine (0.40 g, 0.905 mmol), carbamic acid tert-butyl ester (0.159 g, 1.36 mmol), XantPhos (0.053 g, 0.091 mmol) and K3PO4 (0.384 g, 1.81 mmol) in toluene (9 mL) and water (1.5 mL), was degassed with a stream of argon. Pd2(dba)3 (0.041 g, 0.045 mmol) was then added and the reaction mixture was heated at 85° C. for 2 hours using microwave irradiation and then thermally at 100° C. for 18 hours. After cooling to room temperature, the crude residue was partitioned between water and EtOAc. The aqueous phase was further extracted with EtOAc (×2) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-10% EtOAc in cyclohexane to afford the title compound as an off-white solid (0.352 g, 90% yield). LCMS (Method D): RT=4.68 min, m/z: 430 [M+H+].

Workup

  1. customwas degassed with a stream of argon
  2. custommicrowave irradiation
  3. temperatureAfter cooling to room temperature
  4. customthe crude residue was partitioned between water and EtOAc
  5. extractionThe aqueous phase was further extracted with EtOAc (×2)
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe resultant residue was purified by column chromatography on silica gel eluting with 0-10% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-edb96b26bf2e4bf79ebfb42e2c99fa20
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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