Water → HCID 67298312, compound

HRID 1520321Notes

Reaction equation

HRID 1520321 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17](I)[CH:18]=3)[N:13]=[C:12]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[C:27]([Si:31]([CH3:37])([CH3:36])[O:32][CH2:33][C:34]#[CH:35])([CH3:30])([CH3:29])[CH3:28].C(N(CC)CC)C.O>CN(C=O)C.[Cu]I.C(OCC)(=O)C>[Si:31]([O:32][CH2:33][C:34]#[C:35][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([C:21]1[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=1)[N:11]=[C:10]2[NH:9][C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=1)([C:27]([CH3:28])([CH3:29])[CH3:30])([CH3:36])[CH3:37]

Participants

8

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 3445622tert-Butyl(dimethyl)[(prop-2-yn-1-yl)oxy]silaneHCID 67298145HCID 67298145, compound

Product 1

HCID 67298312HCID 67298312, compoundYield 67%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of N-(3-chloro-4-fluorophenyl)-6-iodo-2-(pyridin-3-yl)quinazolin-4-amine (synthesized as described in Scheme 1 and 4, substituting 5-iodo-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid and 3-chloro-4-fluoroaniline for 2-aminobenzamide) (1.00 g, 2.10 mmol), tert-butyldimethyl(2-propynyloxy)silane (0.85 ml, 4.20 mmol), copper(I) iodide (4.0 mg, 0.021 mmol), dichlorobis(triphenylphosphine) palladium (II) (Pd(PPh3)2Cl2) (29 mg, 0.042 mmol), and triethylamine (1.17 ml, 8.39 mmol) in DMF (15 mL) was stirred overnight at room temperature under argon atmosphere. Water (30 mL) and ethyl acetate (30 mL) were added to the mixture. The resultant precipitate was removed by filtration. The filtrate was extracted with EtOAc (2×50 mL). The combined organic layer was washed with water (1×100 mL) and brine (1×100 mL) and was dried over Na2SO4. After filtration and evaporation, the crude product was obtained, which was purified by column chromatography on silica gel (eluted with hexane/ethyl acetate 6:1 to 1:3) to give 0.73 g of 6-(3-(tert-butyldimethylsilyloxy)prop-1-ynyl)-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine as light brown solid (67%). LCMS m/z=519 (M+1) (Method D) (retention time=3.22 min). 1H NMR (300 MHz, DMSO) δ 9.99 (s, 1H), 9.35 (s, 1H), 8.62-8.44 (m, 3H), 8.11 (dd, J=6.8, 2.6 Hz, 1H), 7.76-7.66 (m, 3H), 7.45-7.30 (m, 2H), 4.48 (s, 2H), 0.75 (s, 9H), 0.16 (s, 6H).

Workup

  1. customThe resultant precipitate was removed by filtration
  2. extractionThe filtrate was extracted with EtOAc (2×50 mL)
  3. washThe combined organic layer was washed with water (1×100 mL) and brine (1×100 mL)
  4. dry with materialwas dried over Na2SO4
  5. filtrationAfter filtration and evaporation
  6. customthe crude product was obtained
  7. customwhich was purified by column chromatography on silica gel (eluted with hexane/ethyl acetate 6:1 to 1:3)

Sources & evidence

ORD record
ord-f92101d4ee3a46939bae642b427f30e4
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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