Methylamine → HCID 20746072, compound

HRID 2308103Notes

Reaction equation

HRID 2308103 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:13][C:12]2[C:7](=[N:8][CH:9]=[CH:10][C:11]=2[O:14][C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19]([CH3:24])=[CH:18]3)[CH:6]=1)=[O:4].C1CCN2[C:28](=[N:29][CH2:30]CC2)CC1.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=[O:38].CN.C([O-])(O)=O.[Na+]>CCOC(C)=O.C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[S:13][C:12]2[C:7](=[N:8][CH:9]=[CH:10][C:11]=2[O:14][C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20]([C:30](=[O:38])[NH:29][CH3:28])[C:19]([CH3:24])=[CH:18]3)[CH:6]=1)=[O:4]

Participants

8

Reactant 5

HCID 6329MethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 821294-Nitrophenyl chloroformateHCID 516892Sodium BicarbonateHCID 20746071HCID 20746071, compound

Product 1

HCID 20746072HCID 20746072, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of methylene chloride (2 mL) was added 7-(2-Methyl-1H-indol-5-yloxy)-thieno[3,2-b]pyridine-2-carboxylic acid methyl ester (0.4 g, 1.82 mmol), DBU (0.5 mL, 3.5 mmol), 4-nitrophenyl chloroformate (0.72 g, 3.5 mmol) then stirred at 0° C. for 24 h. Next was added 2.4 mL of methyl amine (2.0 M in THF) via syringe and stirred an addition 1 h. To the reaction mixture was added 50 mL of EtOAc worked-up by portioning between 50/50 NaHCO3 and concentrated. Purification was through silica (30 mL) eluting with EtOAc/CH2Cl2/MeOH (2:1:0.1) combined purified fraction to afford 7-(2-Methyl-1-methylcarbamoyl-1H-indol-5-yloxy)-thieno[3,2-b]pyridine-2-carboxylic acid methyl ester as yellow solid (0.35 g, 74%). HPLC: Rt 3.96 min. (100% area). 1H NMR (CDCl3-d3, 400 MHz) δ: 8.40 (1H, d, J=5.6 Hz), 8.09 (1H, s), 7.64 (1H, d, J=8.8 Hz), 6.92 (1H, dd, J=7.4, 2.2 Hz), 6.84 (1H, d, J=9.1 Hz), 6.49 (1H, d, J=5.3 Hz), 6.23 (1H, s), 5.98 (1H, d, J=4.5 Hz), 3.89 (3H, s), 3.04 (3H, d, 4.5 Hz), 2.52 (3H, s). LCMS (ACPI) M+H+ m/z: 396.2.

Workup

  1. stirringstirred
  2. additionan addition 1 h
  3. concentrationconcentrated
  4. customPurification
  5. washeluting with EtOAc/CH2Cl2/MeOH (2:1:0.1)
  6. customcombined purified fraction

Sources & evidence

ORD record
ord-9bed36a9162e4c34b0caa961058a4d01
Source dataset
uspto-grants-2004_12
Patent number
US06833456B2

Reaction notes

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