Pyridine → 1-(2,2-Difluoro-benzo[1,3]dioxol-5-yl)-3-[4-(3-dimethylamino-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-urea

HRID 540629

반응식

HRID 540629 반응식
Cl[C:2](OC1C=CC([N+]([O-])=O)=CC=1)=[O:3].N1C=CC=CC=1.[NH2:20][C:21]1[CH:31]=[CH:30][C:24]2[O:25][C:26]([F:29])([F:28])[O:27][C:23]=2[CH:22]=1.CCN(C(C1C=CC=C(C)C=1)=O)CC.[CH3:46][N:47]([CH3:65])[CH2:48][CH2:49][CH2:50][O:51][C:52]1[CH:57]=[CH:56][C:55]([NH2:58])=[CH:54][C:53]=1[C:59]1[N:60]([CH3:64])[N:61]=[CH:62][CH:63]=1>ClCCCl>[F:28][C:26]1([F:29])[O:25][C:24]2[CH:30]=[CH:31][C:21]([NH:20][C:2]([NH:58][C:55]3[CH:56]=[CH:57][C:52]([O:51][CH2:50][CH2:49][CH2:48][N:47]([CH3:46])[CH3:65])=[C:53]([C:59]4[N:60]([CH3:64])[N:61]=[CH:62][CH:63]=4)[CH:54]=3)=[O:3])=[CH:22][C:23]=2[O:27]1

참가 물질

7

반응물 5

HCID 1049PyridineHCID 4284N,N-diethyl-m-toluamideHCID 821294-Nitrophenyl chloroformateHCID 27368935-Amino-2,2-difluoro-1,3-benzodioxoleHCID 231395434-(3-dimethylamino-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenylamine

생성물 1

HCID 231395361-(2,2-Difluoro-benzo[1,3]dioxol-5-yl)-3-[4-(3-dimethylamino-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-urea수율 34%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

To a solution of 4-nitrophenyl chloroformate (55.1 mg, 0.273 mmol) in 1,2-dichloroethane (7 mL) and pyridine (22 μL, 0.272 mmol) was added 5-amino-2,2-difluoro-1,3-benzodioxole (28 μL, 0.241 mmol) and stirred for one hour. A spatula of StratoSpheres PL-DETA resin was added and stirring continued for an additional hour. The resulting mix was filtered (washing with 3 mL 1,2-dichloroethane) into a flask containing 4-(3-dimethylamino-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenylamine (49.7 mg, 0.181 mmol) and stirring continued overnight. The resulting material was purified by HPLC. The product was dried in vacuo to afford Compound 129 as a white solid (29.0 mg, 34%). LCMS m/z (%)=474 (M+H, 100), 1H NMR (400 MHz, DMSO-d6) δ: 8.91 (bs, 1H), 8.61 (bs, 1H), 7.65 (d, J=2.09 Hz, 1H), 7.44 (d, J=1.86 Hz, 1H), 7.44 (dd, J=8.88, 2.82 Hz, 1H), 7.37 (d, J=2.71 Hz, 1H), 7.29 (d, J=8.75 Hz, 1H), 7.09 (d, J=8.95 Hz, 1H), 7.07 (dd, J=8.78, 2.18 Hz, 1H), 623 (d, J=1.81 Hz, 1H), 3.97 (t, J=6.35 Hz, 2H), 3.65 (s, 3H), 2.19 (t, J=7.03 Hz, 2H), 2.07 (s, 6H), 1.77-1.67 (m, 2H).

후처리

  1. stirringstirring
  2. waitcontinued for an additional hour
  3. additionThe resulting mix
  4. filtrationwas filtered
  5. wash(washing with 3 mL 1,2-dichloroethane) into a flask
  6. stirringstirring continued overnight
  7. customThe resulting material was purified by HPLC
  8. customThe product was dried in vacuo

출처 및 근거

ORD 기록
ord-c9390a02fa014fbbb49c4ece2919c6b4
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871797B2

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