4-Iodo-2-methoxynicotinaldehyde → 2-Methyl-4-morpholino-6-nitroaniline

HRID 1354624노트

반응식

HRID 1354624 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-:16])=[O:15])[C:3]=1[NH2:17].IC1C=CN=C(OC)C=1C1NC2C=C(N3CCOCC3)C=C(C)C=2N=1.[H][H].IC1C=CN=C(OC)C=1C=O>CO.[Pd]>[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-:16])=[O:15])[C:3]=1[NH2:17]

참가 물질

6

반응물 3

HCID 100383814-Iodo-2-methoxynicotinaldehydeHCID 21103401HCID 21103401, 화합물HCID 178418361HCID 178418361, 화합물

생성물 1

HCID 116011322-Methyl-4-morpholino-6-nitroaniline

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 887Methanol용매2회

반응 조건

온도
0 °C

실험 절차

2-(4-Iodo-2-methoxy-pyridin-3-yl)-4-methyl-6-morpholin-4-yl-1H-benzoimidazole 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-ddbe8b8ca6334d96b4fa47056b3f7057
출처 데이터셋
uspto-grants-2007_05
특허 번호
US07223757B2

반응 노트

불러오는 중…