Triethylamine → 5-(4-(1-acetyl-5-cyclopropyl-1H-pyrazol-3-ylamino)-5-((trimethylsilyl)ethynyl)pyrimidin-2-yl)-N-(2-(dimethylamino)ethyl)thiophene-2-sulfonamide

HRID 1484923Notes

Reaction equation

HRID 1484923 reaction equation
[C:1]([N:4]1[C:8]([CH:9]2[CH2:11][CH2:10]2)=[CH:7][C:6]([NH:12][C:13]2[C:18](Br)=[CH:17][N:16]=[C:15]([C:20]3[S:24][C:23]([S:25]([NH:28][CH2:29][CH2:30][N:31]([CH3:33])[CH3:32])(=[O:27])=[O:26])=[CH:22][CH:21]=3)[N:14]=2)=[N:5]1)(=[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]([N:4]1[C:8]([CH:9]2[CH2:11][CH2:10]2)=[CH:7][C:6]([NH:12][C:13]2[C:18]([C:42]#[C:41][Si:43]([CH3:46])([CH3:45])[CH3:44])=[CH:17][N:16]=[C:15]([C:20]3[S:24][C:23]([S:25]([NH:28][CH2:29][CH2:30][N:31]([CH3:33])[CH3:32])(=[O:27])=[O:26])=[CH:22][CH:21]=3)[N:14]=2)=[N:5]1)(=[O:3])[CH3:2]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 581695145-(4-(1-acetyl-5-cyclopropyl-1H-pyrazol-3-ylamino)-5-bromopyrimidin-2-yl)-N-(2-(dimethylamino)ethyl)thiophene-2-sulfonamide

Product 1

HCID 581694735-(4-(1-acetyl-5-cyclopropyl-1H-pyrazol-3-ylamino)-5-((trimethylsilyl)ethynyl)pyrimidin-2-yl)-N-(2-(dimethylamino)ethyl)thiophene-2-sulfonamide

Reagents, catalysts & solvents 3

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

Procedure

The mixture of crude 5-(4-(1-acetyl-5-cyclopropyl-1H-pyrazol-3-ylamino)-5-bromopyrimidin-2-yl)-N-(2-(dimethylamino)ethyl)thiophene-2-sulfonamide (from step 4), Pd(PPh3)2Cl2 (14 mg, 0.02 mmol, 0.05 eq) and CuI (8 mg, 0.04 mmol, 0.1 eq) was flushed with nitrogen. Anhydrous THF (12 mL) and Et3N (121 mg, 1.2 mmol, 3.0 eq) were added and the reaction mixture was flushed with nitrogen. Ethynyl-trimethylsilane (118 mg, 1.2 mmol, 3.0 eq) was added and the reaction mixture was stirred at rt for 1 h. Then, the reaction mixture was concentrated to about 5 mL, which was taken in EtOAc and was washed with water, brine. The combined organic layers were concentrated to afford crude 5-(4-(1-acetyl-5-cyclopropyl-1H-pyrazol-3-ylamino)-5-((trimethylsilyl)ethynyl)pyrimidin-2-yl)-N-(2-(dimethylamino)ethyl) thiophene-2-sulfonamide, which was used for the next step without further purification). LC-MS (m/z)=572.0 [M+H]+

Workup

  1. customwas flushed with nitrogen
  2. customthe reaction mixture was flushed with nitrogen
  3. concentrationThen, the reaction mixture was concentrated to about 5 mL, which
  4. washwas washed with water, brine
  5. concentrationThe combined organic layers were concentrated

Sources & evidence

ORD record
ord-8ac62d757d824cc3912f6b5427f71eb5
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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