Sodium Carbonate → 1-[5-(2-Fluoro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol

HRID 1039991노트

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HRID 1039991 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([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:4][C:3]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:35]1[S:39][C:38]([C:40]2([OH:44])[CH2:43][CH2:42][CH2:41]2)=[N:37][CH:36]=1>CN(C=O)C.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=[CH:11][N:10]=2)=[CH:4][C:3]=1[C:35]1[S:39][C:38]([C:40]2([OH:44])[CH2:43][CH2:42][CH2:41]2)=[N:37][CH:36]=1

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 584562241-(5-Bromothiazol-2-yl)cyclobutanolHCID 67258663N-[4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

생성물 1

HCID 584564151-[5-(2-Fluoro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol수율 24.9%

시약·촉매·용매 3

HCID 178418807HCID 178418807, 화합물촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
85 °C

실험 절차

To a solution of the product of Step 2 (383 mg, 1.0 mmol) in DMF (2 mL) and aqueous sodium carbonate (2 M, 1.5 mL, 3.0 mmol) in a microwave vial was added Intermediate 1 (234 mg, 1.0 mmol), and PdCl2(dppf)-dichloromethane adduct (82 mg, 0.1 mmol) under dry nitrogen. The vial was sealed and the reaction was heated in a microwave at 85° C. for 2 hours. The reaction was cooled to room temperature, diluted with ethyl acetate, washed with water, then brine and was dried over sodium sulfate. The organic was concentrated after filtration and was purified by flash chromatography (25:75 ethyl acetate:hexanes) to afford 1-[5-(2-fluoro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol as an off-white foamy solid (102 mg, 0.249 mmol, 24.9%). 1H NMR (500 MHz, CDCl3): δ 8.66 (d, J=4.9 Hz, 1H); 8.07 (s, 1H); 8.03 (d, J=6.1 Hz, 1H); 7.82 (s, 1H); 7.50 (dt, J=8.8, 3.4 Hz, 1H); 7.16 (t, J=9.6 Hz, 1H); 7.07 (d, J=4.9 Hz, 1H); 4.07 (s, 1H); 2.77-2.70 (m, 2H); 2.59-2.49 (m, 2H); 2.13-1.98 (m, 2H). rhSYK activity=++

후처리

  1. customThe vial was sealed
  2. temperatureThe reaction was cooled to room temperature
  3. washwashed with water
  4. dry with materialbrine and was dried over sodium sulfate
  5. concentrationThe organic was concentrated
  6. filtrationafter filtration
  7. customwas purified by flash chromatography (25:75 ethyl acetate:hexanes)

출처 및 근거

ORD 기록
ord-a055fa6bcef24d7ba33a7aa53a2ae64a
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08551984B2

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