Dichloromethane → HCID 53242052, compound

HRID 2369373Notes

Reaction equation

HRID 2369373 reaction equation
Cl[C:2]1[S:3][C:4]([C:15]#[C:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[C:5]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[N:6]=1.[NH2:24][C:25]1[N:30]=[CH:29][C:28](B([O-])OC(C(C)(C)C)C)=[CH:27][N:26]=1.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>CN(C=O)C.O.COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:24][C:25]1[N:30]=[CH:29][C:28]([C:2]2[S:3][C:4]([C:15]#[C:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[C:5]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[N:6]=2)=[CH:27][N:26]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 53242051HCID 53242051, compoundHCID 86671721HCID 86671721, compound

Product 1

HCID 53242052HCID 53242052, compoundYield 25%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

705 mg (2.00 mmol) of tert-butyl N-{2-chloro-5-[2-(4-fluorophenyl)ethynyl]-1,3-thiazol-4-yl}carbamate are dissolved in a mixture of 4 ml of DMF, 2 ml of water and 8 ml of DME together with 663 mg (3.00 mmol) of pinacolyl 2-amino-pyrimidine-5-boronate, and 829 mg (6.00 mmol) of potassium carbonate and 81 mg (0.10 mmol) of Pd(dppf)2Cl2.CH2Cl2 are introduced. Argon is subsequently passed through the reaction mixture for 10 min, the vessel is sealed and heated at 85° C. for 44 h. After cooling, the reaction mixture is extracted twice with saturated NaCl solution, and the aqueous phases are extracted with ethyl acetate. The combined organic phases are dried over sodium sulfate, evaporated in vacuo, and the residue is purified by flash chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1/2; 1% of triethylamine), giving 205 mg (0.49 mmol, 25%) of tert-butyl N-[2-(2-aminopyrimidin-5-yl)-5-[2-(4-fluorophenyl)ethynyl]-1,3-thiazol-4-yl]carbamate as yellow solid; m.p. 201-203;

Workup

  1. customthe vessel is sealed
  2. temperatureAfter cooling
  3. extractionthe reaction mixture is extracted twice with saturated NaCl solution
  4. extractionthe aqueous phases are extracted with ethyl acetate
  5. dry with materialThe combined organic phases are dried over sodium sulfate
  6. customevaporated in vacuo
  7. customthe residue is purified by flash chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1/2; 1% of triethylamine)

Sources & evidence

ORD record
ord-53058e09cad14a019c9bd8e9fa62692d
Source dataset
uspto-grants-2014_04
Patent number
US08703961B2

Reaction notes

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