Oxygen → HCID 59254925, compound

HRID 2194996Notes

Reaction equation

HRID 2194996 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[C:9]1[N:18]=[CH:17][C:16]2[CH2:15][CH2:14][C:13]3[N:19]=[C:20]([NH:22][C:23](=[O:25])[CH3:24])[S:21][C:12]=3[C:11]=2[N:10]=1.[C:26]([CH:28]1[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]1)#[CH:27].C(N(C(C)C)CC)(C)C.O=O>O1CCCC1.Cl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I.ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:27]#[C:26][CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:4][C:3]=1[C:9]1[N:18]=[CH:17][C:16]2[CH2:15][CH2:14][C:13]3[N:19]=[C:20]([NH:22][C:23](=[O:25])[CH3:24])[S:21][C:12]=3[C:11]=2[N:10]=1

Participants

10

Reactant 4

HCID 977OxygenHCID 81531DiisopropylethylamineHCID 15550481tert-Butyl 4-ethynylpiperidine-1-carboxylateHCID 59254920HCID 59254920, compound

Product 1

HCID 59254925HCID 59254925, compound

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 13169693Triphenylphosphine palladium dichlorideCatalystHCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

2.0 g (4.0 mmol) N-[8-(2-chloro-5-iod-phenyl)-4,5-dihydro-thiazolo[4,5-h]quinazolin-2-yl]-acetamide are placed in 50 mL tetrahydrofuran under an argon atmosphere and combined with 1.5 g (7 mmol) tert-butyl 4-ethynyl-piperidine-1-carboxylate and 0.5 ml (3 mmol) diisopropylethylamine. The mixture is kept free from oxygen and 78 mg (0.1 mmol) triphenylphosphine palladium(II)-chloride and 21 mg (0.1 mmol) copper(I)-iodide are added. The mixture is stirred for 5 hours at 80° C. After cooling to ambient temperature the reaction mixture is combined with dichloromethane and washed with dilute ammonia solution. The organic phase is dried and evaporated to dryness. The residue is purified by chromatography, corresponding fractions are combined and freeze-dried. The intermediate product obtained is stirred for 2 hours in ethereal hydrochloric acid, suction filtered and dried. Yield: 65 mg (m.p.: 162° C.; MH+=430; RT=3.72; Method A)

Workup

  1. additionare added
  2. temperatureAfter cooling to ambient temperature the reaction mixture
  3. washwashed with dilute ammonia solution
  4. customThe organic phase is dried
  5. customevaporated to dryness
  6. customThe residue is purified by chromatography, corresponding fractions
  7. customfreeze-dried
  8. customThe intermediate product obtained
  9. filtrationsuction filtered
  10. customdried
  11. customYield: 65 mg (m.p.: 162° C.; MH+=430; RT=3.72; Method A)

Sources & evidence

ORD record
ord-ce38d3b873544439ac29a9b1585fc891
Source dataset
uspto-grants-2012_12
Patent number
US08334378B2

Reaction notes

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