Lithium hydroxide, monohydrate → HCID 178512398, compound

HRID 254363Notes

Reaction equation

HRID 254363 reaction equation
C[O:2][C:3](=[O:34])[CH:4]([NH2:33])[CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]([NH2:32])=[N:20][C:21]([C:23]2[C:28]([NH2:29])=[N:27][C:26]([NH2:30])=[C:25]([Cl:31])[N:24]=2)=[O:22])=[CH:10][CH:9]=1.O.[OH-].[Li+]>CO.C1COCC1.O>[NH2:33][CH:4]([CH2:5][CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]([NH2:32])=[N:20][C:21]([C:23]2[C:28]([NH2:29])=[N:27][C:26]([NH2:30])=[C:25]([Cl:31])[N:24]=2)=[O:22])=[CH:12][CH:13]=1)[C:3]([OH:34])=[O:2]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 178501609HCID 178501609, compound

Product 1

HCID 178512398HCID 178512398, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Amino-4-(4-{4-[N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]butyl}-phenoxy)butyric acid methyl ester (140) (110 mg, 0.223 mmol) was dissolved in a mixture of methanol (1 mL)/THF (1 mL)/water (1 mL). Lithium hydroxide monohydrate (14 mg, 0.334 mmol) was added and the reaction mixture was stirred at room temperature for 16 h before it was concentrated in vacuo. The resulting residue was diluted with water (1 mL), acidified to pH 2 with 1N aqueous HCl, and purified through a DOWEX 50WX 8-200 ion exchange resin eluting with 10% aqueous ammonium hydroxide. The desired product was obtained as a yellow solid (75 mg, 70% yield). 1H NMR (300 MHz, CD3OD) δ 1.55-1.78 (m, 4H), 2.10-2.45 (m, 2H), 2.52-2.65 (m, 2H), 3.30-3.35 (m, 2H), 3.65-3.75 (m, 1H), 4.05-4.15 (m, 2H), 6.85 (d, J=8.5 Hz, 2H), 7.10 (d, J=8.5 Hz, 2H). m/z (ESI) 479 [C20H27ClN8O4+H]+. mp 178-180° C.

Workup

  1. concentrationwas concentrated in vacuo
  2. additionThe resulting residue was diluted with water (1 mL)
  3. custompurified through a DOWEX 50WX 8-200 ion exchange resin
  4. washeluting with 10% aqueous ammonium hydroxide

Sources & evidence

ORD record
ord-25c209b68b3d4bcdbad0d52387ca8536
Source dataset
uspto-grants-2011_01
Patent number
US07875619B2

Reaction notes

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