Diisopropylamine → tert-butyl 5-cyclopropyl-3-(2-phenyl-5-((trimethylsilyl)ethynyl)pyrimidin-4-ylamino)-1H-pyrazole-1-carboxylate

HRID 1484851Notes

Reaction equation

HRID 1484851 reaction equation
[CH:1]1([C:4]2[N:8]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[N:7]=[C:6]([NH:16][C:17]3[C:22](I)=[CH:21][N:20]=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[N:18]=3)[CH:5]=2)[CH2:3][CH2:2]1.N(C(C)C)C(C)C.[Si:37]([C:41]#[CH:42])([CH3:40])([CH3:39])[CH3:38]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1COCC1>[CH:1]1([C:4]2[N:8]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[N:7]=[C:6]([NH:16][C:17]3[C:22]([C:42]#[C:41][Si:37]([CH3:40])([CH3:39])[CH3:38])=[CH:21][N:20]=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[N:18]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 66111TrimethylsilylacetyleneHCID 58169414tert-butyl 5-cyclopropyl-3-(5-iodo-2-phenylpyrimidin-4-ylamino)-1H-pyrazole-1-carboxylate

Product 1

HCID 58169585tert-butyl 5-cyclopropyl-3-(2-phenyl-5-((trimethylsilyl)ethynyl)pyrimidin-4-ylamino)-1H-pyrazole-1-carboxylateYield 118.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Under nitrogen, to the mixture of tert-butyl 5-cyclopropyl-3-(5-iodo-2-phenylpyrimidin-4-ylamino)-1H-pyrazole-1-carboxylate (245 mg, 0.49 mmol, 1.0 equiv), PdCl2(PPh3)2 (40 mg, 0.057 mmol, 0.12 equiv.), CuI (22 mg, 0.115 mmol, 0.23 equiv.), i-Pr2NH (1.7 mL, 11.78 mmol, 24 equiv.) and THF (10 mL), TMS-acetylene (3.5 mL, 25 mmol, 51 equiv.) were added. After stirring at r.t. for 2 h, silica gel was added to the reaction mixture and the solvents were removed. The residue was purified by silica gel chromatography (hexane/EtOAc=3:1 as eluant) afford tert-butyl 5-cyclopropyl-3-(2-phenyl-5-((trimethylsilyl)ethynyl) pyrimidin-4-ylamino)-1H-pyrazole-1-carboxylate (276 mg, 98%). LC-MS (m/z): 474.2 [M+H]+. To the solution of tert-butyl 5-cyclopropyl-3-(2-phenyl-5-((trimethylsilyl)ethynyl)pyrimidin-4-ylamino)-1H-pyrazole-1-carboxylate (276 mg, 0.58 mmol, 1 equiv.) in CH2Cl2 (2 mL) was added TFA (2 mL). After 10 min at rt, the reaction mixture was concentrated to generate crude N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-phenyl-5-((trimethylsilyl)ethynyl)pyrimidin-4-amine, which was used in next step without further purification. LC-MS (m/z): 374.2 [M+H]+.

Workup

  1. additionwere added
  2. additionsilica gel was added to the reaction mixture
  3. customthe solvents were removed
  4. customThe residue was purified by silica gel chromatography (hexane/EtOAc=3:1 as eluant)

Sources & evidence

ORD record
ord-5b9bafa05fc84bf0a877b037e45b80f4
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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