1-Hydroxybenzotriazole → 3-({[2-amino-5-(trifluoromethyl)phenyl]carbamoyl}methyl)-N-methoxy-N-methylcyclobutane-1-carboxamide

HRID 511619노트

반응식

HRID 511619 반응식
[CH3:1][O:2][N:3]([CH3:14])[C:4]([CH:6]1[CH2:9][CH:8]([CH2:10][C:11]([OH:13])=O)[CH2:7]1)=[O:5].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[F:37][C:38]([F:48])([F:47])[C:39]1[CH:40]=[C:41]([NH2:46])[C:42]([NH2:45])=[CH:43][CH:44]=1>C(Cl)Cl>[NH2:45][C:42]1[CH:43]=[CH:44][C:39]([C:38]([F:37])([F:47])[F:48])=[CH:40][C:41]=1[NH:46][C:11]([CH2:10][CH:8]1[CH2:7][CH:6]([C:4]([N:3]([O:2][CH3:1])[CH3:14])=[O:5])[CH2:9]1)=[O:13]

참가 물질

6

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 5208224-Trifluoromethyl-1,2-phenylenediamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 598349352-{3-[Methoxy(methyl)carbamoyl]cyclobutyl}acetic acid

생성물 1

HCID 866661183-({[2-amino-5-(trifluoromethyl)phenyl]carbamoyl}methyl)-N-methoxy-N-methylcyclobutane-1-carboxamide수율 44%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

TEA (1.49 ml, 10.70 mmol) was added to a suspension of 2-{3-[methoxy(methyl)carbamoyl]cyclobutyl}acetic acid, EDC.HCl 1.18 g, 6.20 mmol), HOBt.xH2O (0.77 g, 5.69 mmol) in DCM (20 ml) at 0° C. and stirred for 5 min before the addition of 4-(trifluoromethyl)benzene-1,2-diamine (1.04 g, 10.34 mmol). This was stirred for a further 20 min at 0° C. then allowed to warm to RT. The reaction was monitored by LC MS, after 2 hours the reaction mixture was washed with 1N HCl (50 ml) then sat. NaHCO3 (50 ml). This was dried over Na2SO4, filtered and evaporated to dryness. Purification by silica gel column chromatography, eluting with EtOAc gave the desired product (0.83 g, 44%) as a beige solid; MS (ESI+) for C16H20N3O3 m/z 360.00 [M+H]+; HPLC purirty 90% (ret. time, 1.64 min); 1H NMR (500 MHz, MeOD) δH ppm 2.02-2.16 (2H, m), 2.31-2.68 (4H, m), 2.69-2.88 (1H, m), 3.18 (3H, d, J=4.41 Hz), 3.36-3.59 (1H, m), 3.65-3.76 (3H, m), 6.81-6.97 (1H, m), 7.02-7.27 (1H, m), 7.28-7.48 (1H, m).

후처리

  1. temperatureto warm to RT
  2. waitThe reaction was monitored by LC MS, after 2 hours
  3. washthe reaction mixture was washed with 1N HCl (50 ml)
  4. dry with materialThis was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customPurification by silica gel column chromatography
  8. washeluting with EtOAc

출처 및 근거

ORD 기록
ord-23f2b553f53f47b8a13204f3d4d36477
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096634B2

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