4-Iodo-2-methoxynicotinaldehyde → 2-(4-Iodo-2-methoxy-3-pyridinyl)-7-methyl-5-(4-morpholinyl)-1H-benzimidazole

HRID 1793721노트

반응식

HRID 1793721 반응식
[CH3:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:5]=[C:4]([N+:14]([O-])=O)[C:3]=1[NH2:17].[H][H].[I:20][C:21]1[CH:26]=[CH:25][N:24]=[C:23]([O:27][CH3:28])[C:22]=1[CH:29]=O>CO.[Pd]>[I:20][C:21]1[CH:26]=[CH:25][N:24]=[C:23]([O:27][CH3:28])[C:22]=1[C:29]1[NH:14][C:4]2[CH:5]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[CH:7]=[C:2]([CH3:1])[C:3]=2[N:17]=1

참가 물질

6

반응물 3

HCID 100383814-Iodo-2-methoxynicotinaldehydeHCID 116011322-Methyl-4-morpholino-6-nitroanilineHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 116623782-(4-Iodo-2-methoxy-3-pyridinyl)-7-methyl-5-(4-morpholinyl)-1H-benzimidazole

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 887Methanol용매2회

반응 조건

온도
0 °C

실험 절차

2-Methyl-4-morpholin-4-yl-6-nitro-phenylamine (15.2 g, 64 mmol) was suspended in methanol (200 ml) in a PARR flask. Palladium on carbon (1.0 g, 10% Pd) was added and the suspension shaken under 60 psi of hydrogen overnight. The mixture was filtered through a pad of celite (under argon) into a 3-neck flask, the celite rinsed with methanol and the filtrate diluted with methanol to a total volume of 500 ml and cooled to 0° C. A solution of 4-Iodo-2-methoxy-pyridine-3-carbaldehyde (14.6 g, 55.5 mmol) in methanol (500 ml) was added slowly (during 3 hours). After addition of ˜¼ of the solution the system was opened to air and stirred over the weekend, thereby reaching room temperature. The reaction mixture was concentrated in vacuo, filtered through a pad of silica (eluent: methylenechloride-ethyl acetate-methanol 55-40-5) then crystallized from ethyl acetate. The title compound was isolated as brown solid (12.68 g, 51%). Flash column chromatography of the mother liquor (gave additional 2.90 g (12%). [pack column with methylene chloride, elute compound with methylene chloride-ethyl acetate 6-4, then methylenechloride-ethyl acetate-methanol 58-40-2]. LCMS (M+H)+ m/z 451 (t=1.03 min.). 1H NMR (500 MHz, CDCl3) δ 7.76 (1H, d, J=5.3 Hz),), 7.42 (1H, d, J=5.3 Hz), 6.85 (1H, broad s), 6.82 (1H, s), 3.86 (4H, t, J=4.5 Hz), 3.79 (3H, s), 3.12 (4H, t, J=4.5 Hz), 2.60 (3H, s), 2.21 (3H, s).

후처리

  1. filtrationThe mixture was filtered through a pad of celite (under argon) into a 3-neck flask
  2. washthe celite rinsed with methanol
  3. additionthe filtrate diluted with methanol to a total volume of 500 ml
  4. additionAfter addition of ˜¼ of the solution the system
  5. customreaching room temperature
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. filtrationfiltered through a pad of silica (eluent: methylenechloride-ethyl acetate-methanol 55-40-5)
  8. customthen crystallized from ethyl acetate

출처 및 근거

ORD 기록
ord-8941fe6b357b4ce0a624b54fdaa3df7f
출처 데이터셋
uspto-grants-2006_07
특허 번호
US07081454B2

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