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

HRID 1039991ノート

反応式

HRID 1039991 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
85 °C

実験手順

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=++

後処理

  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)

出典と根拠

ORDレコード
ord-a055fa6bcef24d7ba33a7aa53a2ae64a
出典データセット
uspto-grants-2013_10
特許番号
US08551984B2

反応ノート

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