Trimethylsilylacetylene → 4-{2-ethoxy-6-[2-(trimethylsilyl)ethynyl]-1H-1,3-benzodiazol-1-yl}pyrimidin-2-amine

HRID 1398645Notes

Reaction equation

HRID 1398645 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([O:10][CH2:11][CH3:12])[N:7]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[N:14]=3)[C:6]=2[CH:20]=1.[C:21]([Si:23]([CH3:26])([CH3:25])[CH3:24])#[CH:22]>N1CCCCC1.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>[CH2:11]([O:10][C:8]1[N:7]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[N:14]=2)[C:6]2[CH:20]=[C:2]([C:22]#[C:21][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:3]=[CH:4][C:5]=2[N:9]=1)[CH3:12]

Participants

6

Reactant 2

HCID 66111Trimethylsilylacetylene2×HCID 681818044-(6-Bromo-2-ethoxy-1,3-benzodiazol-1-yl)pyrimidin-2-amine

Product 1

HCID 681816194-{2-ethoxy-6-[2-(trimethylsilyl)ethynyl]-1H-1,3-benzodiazol-1-yl}pyrimidin-2-amine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418397HCID 178418397, compoundCatalyst2×HCID 8082PiperidineSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 4-(6-bromo-2-ethoxy-1H-1,3-benzodiazol-1-yl)pyrimidin-2-amine (270 mg, 0.74 mmol) in piperidine (1.8 mL) was introduced tetrakis(triphenylphosphine)palladium(0) (69 mg, 0.06 mmol), copper(I) iodide (11 mg, 0.06 mmol) and ethynyltrimethylsilane (0.53 mL, 3.71 mmol). The reaction mixture was warmed to 65° C. for 3 hr. After cooling to RT, the reaction mixture was re-treated with further tetrakis(triphenylphosphine)palladium(0) (10 mg, 0.01 mmol), copper(I) iodide (5 mg, 0.03 mmol), ethynyltrimethylsilane (0.20 mL, 1.4 mmol) and warmed to 65° C. for an additional 2 hr. The reaction mixture was concentrated in vacuo and the residue re-dissolved in DCM (10 mL) and re-evaporated to dryness in vacuo (this procedure was repeated twice). Purification of the residue by column chromatography (Biotage, DCM containing a 2-8% gradient of methanol) furnished the title compound as an off-white solid: 1H NMR (250 MHz, DMSO) delta −0.07-0.07 (9 H, m), 1.21 (3H, t, J=7.01 Hz), 4.40 (2H, q, J=7.06 Hz), 6.65-6.81 (1H, m), 6.88 (2H, br. s.), 7.06 (1H, dd, J=8.15, 1.60 Hz), 7.20 (1H, d, J=8.22 Hz), 7.98 (1H, d, J=1.22 Hz), 8.12-8.25 (1H, m); LCMS: m/z=+352.45 (M+H)+.

Workup

  1. temperatureAfter cooling to RT
  2. temperaturewarmed to 65° C. for an additional 2 hr
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. dissolutionthe residue re-dissolved in DCM (10 mL)
  5. customre-evaporated to dryness in vacuo (this procedure
  6. customPurification of the residue by column chromatography (Biotage, DCM containing a 2-8% gradient of methanol)

Sources & evidence

ORD record
ord-236d2508d5f1491e9d73a51f28cb33d2
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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