Dimethylformamide → HCID 68349568, compound

HRID 706808Notes

Reaction equation

HRID 706808 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][CH:9]2[CH2:11][CH2:10]2)=[N:6][CH:7]=1.[CH3:12][Si:13]([C:16]#[CH:17])([CH3:15])[CH3:14].CCN(C(C)C)C(C)C.CN(C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I.O>[CH:9]1([NH:8][C:5]2[N:4]=[CH:3][C:2]([C:17]#[C:16][Si:13]([CH3:15])([CH3:14])[CH3:12])=[CH:7][N:6]=2)[CH2:11][CH2:10]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 50233275-bromo-N-cyclopropylpyrimidin-2-amine

Product 1

HCID 68349568HCID 68349568, compoundYield 95.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

5-Bromo-N-cyclopropylpyrimidin-2-amine (1.06 g, 5 mmol), trimethylsilylacetylene (2.5 g, 25 mmol), Pd(PPh3)4 (289 mg, 0.25 mmol) and CuI (71 mg, 0.375 mmol) were placed in a two neck flask with a rubber plug. The mixture underwent 3 cycles of vacuum and filling with Ar2, a solution of DIPEA (968 mg, 0.45 mmol) and DMF (10 mL) was injected to the flask. The mixture was stirred at 80° C. for 15 hrs, and then was poured into 50 mL water, extracted with EtOAc (30 mL×3), organic layer was washed with brine, dried with Na2SO4, filtered, and the filtrate was evaporated in vacuo. The residue was purified by chromatography on silica gel (PE/EtOAc 82:18 to 64:36) to give 1.1 g N-cyclopropyl-5-(2-(trimethylsilyl)ethynyl)pyrimidin-2-amine. This compound was dissolved in 20 mL CH2Cl2, a solution of TBAF (1.3 g, 5 mmol) in 10 mL CH2Cl2 was added into the above solution. The mixture was stirred at rt for 1 h, evaporated in vacuo. The residue was purified by chromatography on silica gel (PE/EtOAc 82:18 to 64:36) to give 0.55 g product as a pale yellow solid (72.8%). 1H NMR (300 MHz, CDCl3) δ: 8.43 (2 H, s), 5.77 (1 H, brs), 3.18 (1 H, s), 2.76-2.81 (1 H, m), 0.82-0.87 (2 H, m), 0.54-0.59 (2 H, m). LCMS: m/z [M+H]+ 160.0863.

Workup

  1. extractionextracted with EtOAc (30 mL×3), organic layer
  2. washwas washed with brine
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. customthe filtrate was evaporated in vacuo
  6. customThe residue was purified by chromatography on silica gel (PE/EtOAc 82:18 to 64:36)

Sources & evidence

ORD record
ord-6b26329b8d6b4c2285a195f989beffb6
Source dataset
uspto-grants-2015_11
Patent number
US09174996B2

Reaction notes

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