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Triethylamine → 3-(2-(2-((2-Methoxy-4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)benzamide

HRID 2272422
ノート
印刷プレビュー

反応式

HRID 2272422 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:18]=[CH:17][C:16]([CH:19]3[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]3)=[CH:15][C:14]=2[O:32][CH3:33])[N:3]=1.[C:34]([C:36]1[CH:37]=[C:38]([CH:42]=[CH:43][CH:44]=1)[C:39]([NH2:41])=[O:40])#[CH:35].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>CN(C=O)C.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.[Cu]I>[CH3:33][O:32][C:14]1[CH:15]=[C:16]([CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH:17]=[CH:18][C:13]=1[NH:12][C:4]1[N:3]=[C:2]([CH2:35][CH2:34][C:36]2[CH:37]=[C:38]([CH:42]=[CH:43][CH:44]=2)[C:39]([NH2:41])=[O:40])[C:7]([C:8]([F:10])([F:11])[F:9])=[CH:6][N:5]=1
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-Ethynylbenzamide2 回HCID 86675841tert-Butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidine-1-carboxylate

生成物 1

HCID 601621213-(2-(2-((2-Methoxy-4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)benzamide収率 73.1%

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

To a mixture of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidine-1-carboxylate (I34) 0.098 g, 0.20 mmol), 3-ethynylbenzamide (I31) (0.038 g, 0.26 mmol), PdCl2(PPh3)2 (9 mg, 0.01 mmol), triphenylphosphine (0.010 g, 0.04 mmol) and copper(I) iodide (0.009 g, 0.05 mmol) in DMF (2 mL), that had been degassed with nitrogen for 10 minutes, was added triethylamine (0.090 mL, 0.65 mmol). The mixture was degassed with nitrogen then heated to 120° C. for 25 minutes under microwave irradiation. On cooling to room temperature the resulting mixture was left overnight, then an additional portion of 3-ethynylbenzamide (I26) (0.047 g, 0.32 mmol) was added. After degassing with nitrogen the reaction was heated at 120° C. for 25 minutes under microwave irradiation. The volatiles were evaporated under reduced pressure and the residue purified using silica gel column chromatography (20-70% EtOAc/petroleum benzine 40-60° C.) to give the title compound (I35) (0.073 g, 61%) as a yellow solid; 1H NMR (400 MHz, CDCl3) δ 8.66 (s, 1H), 8.35 (d, J=8.3 Hz, 1H), 8.04 (dd, J=1.4, 1.4 Hz, 1H), 8.02 (s, 1H), 7.93 (ddd, J=7.9, 1.8, 1.2 Hz, 1H), 7.80 (m, 1H), 7.53 (m, 1H), 6.88 (dd, J=8.3, 1.6 Hz, 1H), 6.76 (d, J=1.8 Hz, 1H), 4.27 (m, 2H), 3.91 (s, 3H), 2.81 (m, J=12.2 Hz, 2H), 2.64 (tt, J=12.2, 3.4 Hz, 1H), 1.84 (m, 2H), 1.65 (m, 2H), 1.49 (s, 9H). LCMS Method C: rt 6.59 min; m/z 496.1 [(M-Boc)+H]+, 540.0 [(M-t-Bu)+H]+.

後処理

  1. customhad been degassed with nitrogen for 10 minutes
  2. customThe mixture was degassed with nitrogen
  3. temperatureOn cooling to room temperature the resulting mixture
  4. customAfter degassing with nitrogen the reaction
  5. temperaturewas heated at 120° C. for 25 minutes under microwave irradiation
  6. customThe volatiles were evaporated under reduced pressure
  7. customthe residue purified
  8. customsilica gel column chromatography (20-70% EtOAc/petroleum benzine 40-60° C.)

出典と根拠

ORDレコード
ord-e0ba866d82ea47a0a6d20ae4396720f1
出典データセット
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09120761B2

反応ノート

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