2-Methyl-4-morpholino-6-nitroaniline → 2-(5-Chloro-3,6-dimethoxy-pyridazin-4-yl)-4-methyl-6-morpholin-4-yl-1H-benzimidazole

HRID 970358

Reaction equation

HRID 970358 reaction equation
[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].[Cl:18][C:19]1[C:20]([CH:29]=O)=[C:21]([O:27][CH3:28])[N:22]=[N:23][C:24]=1[O:25][CH3:26]>CO.[Pd]>[Cl:18][C:19]1[C:20]([C:29]2[NH:14][C:4]3[CH:5]=[C:6]([N:8]4[CH2:13][CH2:12][O:11][CH2:10][CH2:9]4)[CH:7]=[C:2]([CH3:1])[C:3]=3[N:17]=2)=[C:21]([O:27][CH3:28])[N:22]=[N:23][C:24]=1[O:25][CH3:26]

Participants

5

Reactant 2

HCID 116011322-Methyl-4-morpholino-6-nitroanilineHCID 590202715-Chloro-3,6-dimethoxy-pyridazine-4-carbaldehyde

Product 1

HCID 590202772-(5-Chloro-3,6-dimethoxy-pyridazin-4-yl)-4-methyl-6-morpholin-4-yl-1H-benzimidazole

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Procedure

To a stirred solution of 2-methyl-4-morpholin-4-yl-6-nitro-phenylamine (0.252 g, 1.06 mmol) in methanol (15 mL) was added 10% palladium on carbon (25 mg) and the suspension flushed well with nitrogen, followed by hydrogen. The resulting suspension was stirred 8 hours at room temperature under an atmosphere of hydrogen (ca. 1 atm). The resulting suspension was filtered under nitrogen through a pad of Celite and washed with methanol (25 mL). This solution was cooled down to 0° C., the 5-chloro-3,6-dimethoxy-pyridazine-4-carbaldehyde (0.225 g, 1.12 mmol) in methanol (10 mL) was added and the reaction mixture was stirred exposed to air at 23° C. for 18 hours. MeOH was evaporated in vacuo and the crude material was purified by preparative HPLC (see method below) to give the title compound as a yellow solid. (0.265 g, 64%) HPLC: 99% (220 nm), LCMS (+ESI, M+H+) m/z 390, IR (KBr, cm−1) 3421, 2956, 2852, 1625, 1470, 1362; 1H NMR (400 MHz, CDCl3) δ 9.99 (s, 1H), 7.17 (s, 0.3H) 6.88 (s, 0.3H), 6.80 (s, 0.7H), 6.74 (s, 0.7H), 4.14 (s, 0.9H), 4.13 (s, 0.9H), 4.12 (s, 2.2H), 4.11 (s,2.2H), 3.83 (m, 4H), 3.13 (m, 4H), 2.62 (s, 2.2H), 2.48 (s, 0.9H). Procedure for the Preparation of 2-(4-chloro-2,6-dimethoxy-pyrimidin-5-yl)-4-methyl-6-morpholin-4-yl-1H-benzimidazole

Workup

  1. customthe suspension flushed well with nitrogen
  2. filtrationThe resulting suspension was filtered under nitrogen through a pad of Celite
  3. washwashed with methanol (25 mL)
  4. temperatureThis solution was cooled down to 0° C.
  5. stirringthe reaction mixture was stirred
  6. waitexposed to air at 23° C. for 18 hours
  7. customMeOH was evaporated in vacuo
  8. customthe crude material was purified by preparative HPLC (see method below)

Sources & evidence

ORD record
ord-d5a08ab9779444baaeec6ce95cda146e
Source dataset
uspto-grants-2007_12
Patent number
US07312215B2

Linked notes

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