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Triethylamine → Tert-butyl 4-(4-((4-((3-carbamoylphenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate

HRID 1485281
ノート
印刷プレビュー

反応式

HRID 1485281 の反応式
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:32]=[CH:31][C:16]([CH2:17][N:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)=[CH:15][CH:14]=2)[N:3]=1.[C:33]([C:35]1[CH:36]=[C:37]([CH:41]=[CH:42][CH:43]=1)[C:38]([NH2:40])=[O:39])#[CH:34].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C>[C:38]([C:37]1[CH:36]=[C:35]([C:33]#[C:34][C:2]2[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]3[CH:32]=[CH:31][C:16]([CH2:17][N:18]4[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]4)=[CH:15][CH:14]=3)[N:3]=2)[CH:43]=[CH:42][CH:41]=1)(=[O:39])[NH2:40]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 120650003-EthynylbenzamideHCID 86675725tert-Butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate

生成物 1

HCID 71208949Tert-butyl 4-(4-((4-((3-carbamoylphenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate収率 29%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

tert-Butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate (I94) (0.30 g, 0.64 mmol), 3-ethynylbenzamide (I144) (102 mg, 0.70 mmol), copper(I) iodide (12 mg, 10 mol %), triphenylphosphine (17 mg, 10 mol %), bis(triphenylphosphine)palladium(II) chloride (22 mg, 5 mol %), DMF (3 mL) and triethylamine (0.443 mL, 3.18 mmol) were loaded into a microwave tube and degassed with nitrogen for five minutes. The resulting mixture was heated under microwave irradiation at 120° C. for 15 minutes then cooled to room temperature. The cooled mixture was added to 5% aqueous potassium carbonate (150 mL) and the resulting mixture extracted with ethyl acetate (3×150 mL). The combined ethyl acetate phases were washed with water (200 mL), brine (200 mL), dried then evaporated. The residue was chromatographed (Biotage Isolera: 12 g silica cartridge, 20-100% ethyl acetate/petroleum benzine 40-60° C. then 0-10% methanol/ethyl acetate) to give the title compound (I145) (107 mg, 29% yield) as a yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.46 (s, 1H), 8.84 (s, 1H), 8.17 (s, 1H), 8.09 (t, J=1.7 Hz, 1H), 8.04 (dt, J=7.9, 1.4 Hz, 1H), 7.77 (dt, J=7.8, 1.3 Hz, 1H), 7.71-7.66 (m, 2H), 7.66-7.52 (m), 7.27 (d, J=8.6 Hz, 2H), 3.44 (s, 2H), 2.33-2.26 (m, 4H), 1.38 (s, 9H). LCMS Method C: rt 5.06 min; m/z 581.1 [M+H]+, 525.1 [M-tBu+2H]+; m/z 579.2 [M−H]−.

後処理

  1. customdegassed with nitrogen for five minutes
  2. temperaturethen cooled to room temperature
  3. additionThe cooled mixture was added to 5% aqueous potassium carbonate (150 mL)
  4. extractionthe resulting mixture extracted with ethyl acetate (3×150 mL)
  5. washThe combined ethyl acetate phases were washed with water (200 mL), brine (200 mL)
  6. customdried
  7. customthen evaporated
  8. customThe residue was chromatographed (Biotage Isolera

出典と根拠

ORDレコード
ord-b0028d489ff2417c9f80c7ad72798991
出典データセット
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09421205B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート