Triethylamine → HCID 58169222, compound

HRID 1484929Notes

Reaction equation

HRID 1484929 reaction equation
[C:1]([NH:4][CH2:5][CH2:6][NH:7][C:8]([C:10]1[S:11][C:12]([C:15]2[N:20]=[C:19]([NH:21][C:22]3[CH:26]=[C:25]([CH:27]4[CH2:29][CH2:28]4)[N:24]([C:30](=[O:32])[CH3:31])[N:23]=3)[C:18](Br)=[CH:17][N:16]=2)=[CH:13][CH:14]=1)=[O:9])(=[O:3])[CH3:2].CCN(CC)CC.[C:41]([Si:43]([CH3:46])([CH3:45])[CH3:44])#[CH:42]>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>[C:1]([NH:4][CH2:5][CH2:6][NH:7][C:8]([C:10]1[S:11][C:12]([C:15]2[N:20]=[C:19]([NH:21][C:22]3[CH:26]=[C:25]([CH:27]4[CH2:29][CH2:28]4)[N:24]([C:30](=[O:32])[CH3:31])[N:23]=3)[C:18]([C:42]#[C:41][Si:43]([CH3:46])([CH3:45])[CH3:44])=[CH:17][N:16]=2)=[CH:13][CH:14]=1)=[O:9])(=[O:3])[CH3:2]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 58169517HCID 58169517, compound

Product 1

HCID 58169222HCID 58169222, compoundYield 35.2%

Reagents, catalysts & solvents 3

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

Procedure

Step 5 A mixture of N-(2-acetamidoethyl)-5-(4-(1-acetyl-5-cyclopropyl-1H-pyrazol-3-ylamino)-5-bromopyrimidin-2-yl)thiophene-2-carboxamide (294.0 mg, 0.5 mmol, 1.0 eq), Pd(PPh3)2Cl2 (40.8 mg, 0.5 mmol, 0.1 eq) and CuI (9.5 mg, 0.05 mmol, 0.1 eq) was flushed with nitrogen. Anhydrous THF (10 mL) and Et3N (154.5 mg, 1.5 mmol, 3.0 eq) were added and the reaction mixture was flushed with nitrogen. Ethynyltrimethylsilane (149.9 mg, 1.5 mmol, 3.0 equiv.) was added and the reaction mixture was stirred at room temperature for 1 h. Then, the reaction mixture was concentrated to 5 mL. The conc. liquid was extracted with EtOAc and washed with water, brine. The organic layers were concentrated to afford the residue, which was purified by silica gel chromatography (PE/EA/MeOH=2:1:0.06 as eluant) to afford N-(2-acetamidoethyl)-5-(4-(1-acetyl-5-cyclopropyl-1H-pyrazol-3-ylamino)-5-((trimethylsilyl)ethynyl) pyrimidin-2-yl)thiophene-2-carboxamide (96.1 mg, 35.2%) as pale yellow solid. LC-MS (m/z)=549.9 [M+H]+

Workup

  1. customwas flushed with nitrogen
  2. customthe reaction mixture was flushed with nitrogen
  3. concentrationThen, the reaction mixture was concentrated to 5 mL
  4. extractionThe conc. liquid was extracted with EtOAc
  5. washwashed with water, brine
  6. concentrationThe organic layers were concentrated
  7. customto afford the residue, which
  8. customwas purified by silica gel chromatography (PE/EA/MeOH=2:1:0.06 as eluant)

Sources & evidence

ORD record
ord-a6e3d641b0b542ed8c19df269ed2c3e8
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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