Triethylamine → 4-[2-Chloro-4-(1-ethyl-propylamino)-pyrimidin-5-yl]-but-3-yn-2-ol

HRID 2189325Notes

Reaction equation

HRID 2189325 reaction equation
Br[C:2]1[C:3]([NH:9][CH:10]([CH2:13][CH3:14])[CH2:11][CH3:12])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH3:15][CH:16]([OH:19])[C:17]#[CH:18].C(N(CC)CC)C>CN(C=O)C.C(Cl)Cl.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>[Cl:8][C:5]1[N:4]=[C:3]([NH:9][CH:10]([CH2:13][CH3:14])[CH2:11][CH3:12])[C:2]([C:18]#[C:17][CH:16]([OH:19])[CH3:15])=[CH:7][N:6]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 162393-Butyn-2-olHCID 580158915-bromo-2-chloro-N-(pentan-3-yl)pyrimidin-4-amine

Product 1

HCID 866373494-[2-Chloro-4-(1-ethyl-propylamino)-pyrimidin-5-yl]-but-3-yn-2-olYield 54.4%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
55 °C

Procedure

To a mixture of (5-bromo-2-chloro-pyrimidin-4-yl)-(1-ethyl-propyl)-amine (0.44 g, 1.58 mmol), Pd(Ph3P)2Cl2 (0.11 g, 0.16 mmol), and CuI (0.03 g, 0.16 mmol) in DMF (14 mL) is added 3-butyn-2-ol (0.19 mL, 2.37 mmol) and triethylamine (0.44 mL, 3.16 mmol). The reaction mixture is stirred at 55° C. for 16 h, diluted with CH2Cl2, filtered through a pad of Celite, and concentrated in vacuo. Purification by flash chromatography (SiO2, EtOAc/Hexane 1:3) gave 0.23 g of 4-[2-chloro-4-(1-ethyl-propylamino)-pyrimidin-5-yl]-but-3-yn-2-ol as yellowish oil.

Workup

  1. filtrationfiltered through a pad of Celite
  2. concentrationconcentrated in vacuo
  3. customPurification by flash chromatography (SiO2, EtOAc/Hexane 1:3)

Sources & evidence

ORD record
ord-4026a3e2b21a4241b3be186b505cb193
Source dataset
uspto-grants-2012_12
Patent number
US08324225B2

Reaction notes

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