Methylamine → Gsk-207040

HRID 222694Notes

Reaction equation

HRID 222694 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[C:13]([O:16][C:17]4[N:18]=[CH:19][C:20]([C:23](Cl)=[O:24])=[N:21][CH:22]=4)[CH:14]=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[CH3:26][NH2:27]>ClCCl>[CH3:26][NH:27][C:23]([C:20]1[CH:19]=[N:18][C:17]([O:16][C:13]2[CH:14]=[CH:15][C:8]3[CH2:7][CH2:6][N:5]([CH:1]4[CH2:4][CH2:3][CH2:2]4)[CH2:11][CH2:10][C:9]=3[CH:12]=2)=[CH:22][N:21]=1)=[O:24]

Participants

4

Reactant 2

HCID 6329MethylamineHCID 866032205-(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy)-pyrazine-2-carbonyl chloride

Product 1

HCID 10473209Gsk-207040

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The product of Example 123, step 1 (1.59 mmol) in dry dichloromethane (10 ml) was treated with methylamine (5 ml, 10 mmol, 2M solution in THF) and stirred at room temperature for 18 hours. The mixture was reduced in vacuo and the resulting crude material was applied to a SCX ion exchange cartridge (Varian bond-elute, 10 g) and washed with methanol and then a mixture of 0.880 ammonia:methanol (1:9). The basic fractions were then reduced and the crude product purified by column chromatography eluting with a mixture of 0.880 ammonia:ethanol:dichloromethane (0.2:1.8:98 and then 0.4:3.6:96) to afford the title compound (E125). 1H NMR (CDCl3) δ 8.91 (1H, d, 1.3 Hz), 8.26 (1H, d, 1.3 Hz), 7.61 (1H, br quartet, 4.8 Hz), 7.15 (1H, m), 6.92 (2H, m), 3.03 (3H, d, 5.1 Hz), 2.93 (4H, m), 2.79 (1H, m), 2.47 (4H, m), 2.08 (2H, m), 1.91 (2H, m), 1.70-1.62 (2H, m).

Workup

  1. washwashed with methanol
  2. additiona mixture of 0.880 ammonia:methanol (1:9)
  3. customthe crude product purified by column chromatography
  4. washeluting with a mixture of 0.880 ammonia:ethanol:dichloromethane (0.2:1.8:98

Sources & evidence

ORD record
ord-77852c62e6d9479bb44de500008e700a
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Reaction notes

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