Methanol → HCID 10126036, compound

HRID 1838311Notes

Reaction equation

HRID 1838311 reaction equation
C[Al](C)C.[NH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1.C([O:14][C:15]([C:17]1[C:21]2=[N:22][C:23]([O:26][CH:27]3[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]3)=[CH:24][CH:25]=[C:20]2[NH:19][CH:18]=1)=O)C.CO>C1(C)C=CC=CC=1.ClCCCl>[N:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[NH:5][C:15]([C:17]1[C:21]2=[N:22][C:23]([O:26][CH:27]3[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]3)=[CH:24][CH:25]=[C:20]2[NH:19][CH:18]=1)=[O:14]

Participants

7

Reactant 4

HCID 887MethanolHCID 104392-AminopyridineHCID 16682925TrimethylaluminumHCID 60060171HCID 60060171, compound

Product 1

HCID 10126036HCID 10126036, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 1140TolueneSolvent

Procedure

AlMe3 (0.3 mL, 0.59 mmol, 2 M in PhCH3) is added to a solution of 2-aminopyridine (56 mg, 0.59 mmol) in toluene (1.0 mL) and 1,2-dichloroethane (1.0 mL) at room temperature. The resulting solution is stirred for 30 minutes at room temperature, 5-(1-methyl-piperidin-4-yloxy)-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid ethyl ester (60 mg, 0.20 mmol) is then added. The resulting mixture is heated at 100° C. for a period of 3 h. The mixture is cooled to room temperature and Na2SO4.10H2O (285 mg, 0.89 mmol) is added. The mixture is stirred for 30 minutes and MeOH (5 mL) is added. The resulting mixture is filtered through a pad of celite and washed with MeOH (3×5 mL) and CHCl3 (3×5 mL). The filtrate is concentrated and purified by chromatography on silica (gradient elution with 5% MeOH/CHCl3 with 0.1% NH4OH to 8% MeOH/CHCl3 with 0.1% NH4OH to 10% MeOH/CHCl3 with 0.1% NH4OH) to give the title compound as a light yellow solid: (Cmp. #1) 1H NMR (400 MHz, CD3OD) δ 8.29-8.27 (m, 2H), 8.01 (s, 1H), 7.73-7.69 (m, 2H), 7.03 (dd, 1H, J=7.1, 5.4 Hz), 6.63 (d, 1H, J=8.7 Hz), 5.40-5.34 (m, 1H), 2.86-2.80 (m, 2H), 2.57-2.52 (m, 2H), 2.35 (s, 3H), 2.30-2.26 (m, 2H), 1.91-1.86 (m, 2H); 13C NMR (100 MHz, CD3OD) δ 163.9, 159.5, 152.4, 148.1, 139.1, 138.2, 131.6, 125.1, 124.1, 119.5, 114.2, 109.3, 107.2, 70.8, 53.6, 45.7, 30.8; MS (CI) m/z 352.3 (M+1).

Workup

  1. temperatureThe resulting mixture is heated at 100° C. for a period of 3 h
  2. temperatureThe mixture is cooled to room temperature
  3. stirringThe mixture is stirred for 30 minutes
  4. filtrationThe resulting mixture is filtered through a pad of celite
  5. washwashed with MeOH (3×5 mL) and CHCl3 (3×5 mL)
  6. concentrationThe filtrate is concentrated
  7. custompurified by chromatography on silica (gradient elution with 5% MeOH/CHCl3 with 0.1% NH4OH to 8% MeOH/CHCl3 with 0.1% NH4OH to 10% MeOH/CHCl3 with 0.1% NH4OH)

Sources & evidence

ORD record
ord-09726d69dcfd4637b3702a806a627ba2
Source dataset
uspto-grants-2004_01
Patent number
US06673811B1

Reaction notes

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