Hydrochloric Acid → 4-(2-(6-Chloropyridin-3-ylamino)pyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621425

반응식

HRID 1621425 반응식
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH2:11][C:12]1[CH:13]=[CH:14][C:15]([Cl:18])=[N:16][CH:17]=1.F[C:20]1[C:25]([C:26]2[N:31]=[C:30]([CH3:32])[N:29]=[C:28]([N:33]([CH2:43][C:44]3[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][CH:45]=3)[CH2:34][C:35]3[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=3)[N:27]=2)=[CH:24][CH:23]=[CH:22][N:21]=1.Cl>C1COCC1.CCOC(C)=O.O>[Cl:18][C:15]1[N:16]=[CH:17][C:12]([NH:11][C:20]2[C:25]([C:26]3[N:31]=[C:30]([CH3:32])[N:29]=[C:28]([N:33]([CH2:34][C:35]4[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=4)[CH2:43][C:44]4[CH:45]=[CH:46][C:47]([O:50][CH3:51])=[CH:48][CH:49]=4)[N:27]=3)=[CH:24][CH:23]=[CH:22][N:21]=2)=[CH:13][CH:14]=1

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 793055-Amino-2-chloropyridine2회HCID 2733832Lithium Hexamethyldisilazide2회HCID 595482404-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

생성물 1

HCID 595482274-(2-(6-Chloropyridin-3-ylamino)pyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine수율 70.2%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
50 °C

실험 절차

1.0 M LHMDS in THF (600 μL, 0.600 mmol) was added to a solution of 5-amino-2-chloropyridine (49 mg, 0.381 mmol) and 4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (80 mg, 0.180 mmol) in THF (4 mL) under nitrogen at rt. A dark orange mixture formed. After 1.5 h, the mixture was heated to about 50° C. After overnight, more 5-amino-2-chloropyridine (49 mg, 0.381 mmol) and LHMDS (600 μL, 0.600 mmol) were added. The reaction mixture was heated for another 2 h and cooled to rt. The mixture was neutralized with HCl (5N, 0.3 mL) and diluted with EtOAc (10 mL) and water (10 mL). The aqueous layer was extracted with DCM twice and the combined organic was dried over Na2SO4 and concentrated. The residue was purified on silica (10-80% EtOAc in hexane) to give a yellow oil (70 mg). LCMS (ES, pos.): calcd for C30H28FN7O2: 553.2. found: 554.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 12.19 (s, 1H); 8.84 (dd, J=7.83, 1.76 Hz, 1H); 8.47 (d, J=2.74 Hz, 1H); 8.33 (dd, J=4.70, 1.76 Hz, 1H); 8.26 (dd, J=8.71, 2.84 Hz, 1H); 7.16-7.24 (m, 5H); 6.80-6.91 (m, 5H); 4.84 (s, 4H); 3.80 (d, J=5.87 Hz, 6H); 2.59 (s, 3H).

후처리

  1. customA dark orange mixture formed
  2. waitAfter overnight
  3. temperatureThe reaction mixture was heated for another 2 h
  4. temperaturecooled to rt
  5. extractionThe aqueous layer was extracted with DCM twice
  6. dry with materialthe combined organic was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified on silica (10-80% EtOAc in hexane)

출처 및 근거

ORD 기록
ord-422c8631fcc245159e2ecc5d395ffa3c
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772480B2

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