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

HRID 410543노트

반응식

HRID 410543 반응식
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

참가 물질

8

반응물 3

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

생성물 1

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

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-3f57268fffb5432db148d9296875ba2e
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759366B2

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