2-Methyl-3-butyn-2-ol → 2-Methyl-4-{5-[2-(2,2,6,6-tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-thiophen-2-yl}-but-3-yn-2-ol

HRID 1434953Notes

Reaction equation

HRID 1434953 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH:14]3[CH2:19][C:18]([CH3:21])([CH3:20])[NH:17][C:16]([CH3:23])([CH3:22])[CH2:15]3)[N:8]=2)=[CH:4][CH:3]=1.[CH3:24][C:25]([OH:29])([C:27]#[CH:28])[CH3:26]>C(N(CC)CC)C.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>[CH3:24][C:25]([OH:29])([C:27]#[C:28][C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH:14]3[CH2:19][C:18]([CH3:21])([CH3:20])[NH:17][C:16]([CH3:23])([CH3:22])[CH2:15]3)[N:8]=2)=[CH:4][CH:3]=1)[CH3:26]

Participants

6

Reactant 2

HCID 82582-Methyl-3-butyn-2-olHCID 57936128{4-[5-Bromothiophen-2-yl]-pyrimidin-2-yl}-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine

Product 1

HCID 113839722-Methyl-4-{5-[2-(2,2,6,6-tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-thiophen-2-yl}-but-3-yn-2-ol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

{4-[5-Bromothiophen-2-yl]-pyrimidin-2-yl}-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine, described in Example 5, (300 mg, 0.76 mmol), PdCl2(PPh3)2 (18 mg, 0.025 mmol), 2-methyl-but-3-yn-2-ol (0.3 ml, 2.53 mmol) and CuI (15 mg) were dissolved in triethylamine (25 ml) and refluxed for 1 hour. The reaction mixture was evaporated, taken up in water and extracted 3 times with TBME. The combined organic phases were dried over sodium sulfate, filtered, and purified via chromatography on silicagel (DCM/MeOH/ammonia:95/5/1 to 90/10/1) to give the title compound as white solid, which was crystallized as HCl-salt from EtOH/HCl. Yield: 150 mg (32%).

Workup

  1. temperaturerefluxed for 1 hour
  2. customThe reaction mixture was evaporated
  3. extractionextracted 3 times with TBME
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. filtrationfiltered
  6. custompurified via chromatography on silicagel (DCM/MeOH/ammonia:95/5/1 to 90/10/1)

Sources & evidence

ORD record
ord-560bdfe8696b4dd88bcaeae9122f7f5a
Source dataset
uspto-grants-2009_11
Patent number
US07615562B2

Reaction notes

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