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

HRID 705755
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HRID 705755 반응식
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:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[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>[C:39]([C:38]1[CH:37]=[C:36]([C:34]#[C:35][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:18]=[CH:17][C:16]([CH:19]4[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]4)=[CH:15][C:14]=3[O:32][CH3:33])[N:3]=2)[CH:44]=[CH:43][CH:42]=1)(=[O:40])[NH2:41]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 120650003-Ethynylbenzamide2회HCID 86675841tert-Butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidine-1-carboxylate

생성물 1

HCID 71225437Tert-butyl 4-(4-((4-((3-carbamoylphenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperidine-1-carboxylate
수율 61.3%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매

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온도
120 °C

실험 절차

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]+.

후처리

  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.)

출처 및 근거

ORD 기록
ord-8aff74749ad3482c8dc1788705ad4084
출처 데이터셋
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09174946B2

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