Trifluoroacetic acid → (R)-(2-(2-amino-3-(3-methylmorpholino)quinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone

HRID 1028970노트

반응식

HRID 1028970 반응식
Br[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1)=[O:10].COC1C=CC(C[NH:23][C:24]2[C:33]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][C@H:35]3[CH3:40])=[CH:32][C:31]3[C:26](=[CH:27][CH:28]=[C:29](B4OC(C)(C)C(C)(C)O4)[CH:30]=3)[N:25]=2)=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(CCC)=CC(CCC)=CC=2CCC)CCCCC1.C(O)(C(F)(F)F)=O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:23][C:24]1[C:33]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][C@H:35]2[CH3:40])=[CH:32][C:31]2[C:26](=[CH:27][CH:28]=[C:29]([C:2]3[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=3[C:9]([N:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)=[O:10])[CH:30]=2)[N:25]=1

참가 물질

7

반응물 5

HCID 6422Trifluoroacetic acidHCID 62657Potassium Phosphate, TribasicHCID 21081571Dicyclohexyl(2',4',6'-tripropyl-[1,1'-biphenyl]-2-yl)phosphineHCID 665791491-(2-Bromo-3-methylbenzoyl)pyrrolidineHCID 71253179(R)-N-(4-methoxybenzyl)-3-(3-methylmorpholino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

생성물 1

HCID 53328994(R)-(2-(2-amino-3-(3-methylmorpholino)quinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

반응 조건

온도
140 °C

실험 절차

A mixture of (2-bromo-3-methylphenyl)(pyrrolidin-1-yl)methanone (0.115 g, 0.429 mmol), (R)—N-(4-methoxybenzyl)-3-(3-methylmorpholino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.07 g, 0.143 mmol), potassium phosphate, anhydrous (0.121 g, 0.572 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′,-tri-1-propyl-1,1′-biphenyl (0.014 g, 0.029 mmol), and Pd2(dba)3 (0.013 g, 0.014 mmol) was purged with N2 followed by the addition of degassed dioxane (1 mL) and degassed water (0.5 mL). The resulting mixture was heated in microwave at 140° C. for 12 min. The reaction went to completion and it was filtered, concentrated, and chromatographed on silica gel using 0-5% MeOH/DCM to afford a yellow oil. To the product was added TFA (10 mL, 130 mmol) and the solution was heated at 60° C. for 18 h until the starting material was consumed. The mixture was concentrated and chromatographed on silica gel using 0-5% 2 M NH3 in MeOH/DCM to afford a yellow solid as (R)-(2-(2-amino-3-(3-methylmorpholino)quinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone. MS (ESI, pos. ion) m/z: 431 (M+1).

후처리

  1. customwas purged with N2
  2. additionfollowed by the addition of degassed dioxane (1 mL)
  3. customdegassed water (0.5 mL)
  4. filtrationwas filtered
  5. concentrationconcentrated
  6. customchromatographed on silica gel using 0-5% MeOH/DCM
  7. customto afford a yellow oil
  8. temperaturethe solution was heated at 60° C. for 18 h until the starting material
  9. customwas consumed
  10. concentrationThe mixture was concentrated
  11. customchromatographed on silica gel using 0-5% 2 M NH3 in MeOH/DCM

출처 및 근거

ORD 기록
ord-9fab89c868fb4869a0dda607c1ba3c5e
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08735384B2

반응 노트

불러오는 중…