Ethylmorpholine → Gsk-554418A

HRID 733693Notes

Reaction equation

HRID 733693 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:14]3[CH:15]=[CH:16][N:17]([CH3:18])[C:13]=3[C:12]([C:19](O)=[O:20])=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.ON1C2C=CC=CC=2N=N1.C([N:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1)C.Cl.C(N=C=NCCCN(C)C)C.N1CCOCC1>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:14]3[CH:15]=[CH:16][N:17]([CH3:18])[C:13]=3[C:12]([C:19]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[O:20])=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 7525EthylmorpholineHCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 44475510HCID 44475510, compound

Product 1

HCID 11501580Gsk-554418A

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-[(3-chlorophenyl)amino]-1-methyl-1H-pyrrolo[3,2-c]pyridine-7-carboxylic acid (25.0 g) in dry dimethylformamide (300 ml), was treated with 1-hydroxybenzotriazole (14.00 g), N-ethylmorpholine (42 ml), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (19.03 g) and morpholine (14.4 ml) at 23° C. under argon with stirring. After 24 h, the solution was evaporated in vacuo and treated with aqueous saturated sodium carbonate (200 ml) and water (300 ml). The mixture was extracted with ethyl acetate (5×200 ml), and the combined, dried (Na2SO4) organic extracts were evaporated in vacuo. The residue was purified by column chromatography on a Biotage silica column (800 g) eluting with ethyl acetate-hexane (1:1 to 7:3) to give the free base of the title compound (26.9 g). A portion of the free base (21.9 g) in methanol (250 ml) was treated with 1.0M hydrochloric acid in diethyl ether to pH1 and then evaporated in vacuo. Trituration of the residue with ether followed by filtration yielded the title compound (22.75 g).

Workup

  1. customthe solution was evaporated in vacuo
  2. additiontreated with aqueous saturated sodium carbonate (200 ml) and water (300 ml)
  3. extractionThe mixture was extracted with ethyl acetate (5×200 ml)
  4. dry with materialdried (Na2SO4) organic extracts
  5. customwere evaporated in vacuo
  6. customThe residue was purified by column chromatography on a Biotage silica column (800 g)
  7. washeluting with ethyl acetate-hexane (1:1 to 7:3)

Sources & evidence

ORD record
ord-d617bdefa66d4f54a0202b0d043caa62
Source dataset
uspto-grants-2009_09
Patent number
US07589206B2

Reaction notes

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