Trimethylsilylacetylene → 2-[5-(3-{[4-(Trifluoromethyl)pyrimidin-2-yl]amino}-5-[(trimethylsilyl)ethynyl]phenyl)-1,3-thiazol-2-yl]propan-2-ol

HRID 410543Notes

Reaction equation

HRID 410543 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]([OH:27])([CH3:26])[CH3:25])=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.[CH3:28][Si:29]([C:32]#[CH:33])([CH3:31])[CH3:30].CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C.[Cu]I.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>[F:16][C:15]([F:18])([F:17])[C:13]1[CH:12]=[CH:11][N:10]=[C:9]([NH:8][C:6]2[CH:5]=[C:4]([C:19]3[S:23][C:22]([C:24]([OH:27])([CH3:26])[CH3:25])=[N:21][CH:20]=3)[CH:3]=[C:2]([C:33]#[C:32][Si:29]([CH3:31])([CH3:30])[CH3:28])[CH:7]=2)[N:14]=1

Participants

8

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 672565992-[5-(3-Bromo-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propan-2-ol

Product 1

HCID 672575982-[5-(3-{[4-(Trifluoromethyl)pyrimidin-2-yl]amino}-5-[(trimethylsilyl)ethynyl]phenyl)-1,3-thiazol-2-yl]propan-2-olYield 68%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of the product of Step 1 (50 mg, 0.109 mmol), trimethylsilylacetylene (30.6 μL, 0.218 mmol), DIPEA (57 μL, 0.33 mmol), CuI (4.2 mg, 0.022 mmol) and Pd(PPh3)4 (12.6 mg, 0.011 mmol) in DMF (2.0 mL) was heated to 85° C. overnight. After cooling to room temperature, the mixture was diluted with ethyl acetate (30 mL) and washed with 1:1 water:brine (2×30 mL). The aqueous layers were further extracted with ethyl acetate (30 mL), then the combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo. Purification by chromatography on silica gel (100:0 to 50:50, hexanes:ethyl acetate) provided 35 mg (0.073 mmol, 68%) of 2-[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-5-[(trimethylsilyl)ethynyl]phenyl)-1,3-thiazol-2-yl]propan-2-ol as a yellow oil.

Workup

  1. washwashed with 1:1 water
  2. extractionThe aqueous layers were further extracted with ethyl acetate (30 mL)
  3. dry with materialthe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by chromatography on silica gel (100:0 to 50:50, hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-3f57268fffb5432db148d9296875ba2e
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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