Hydrochloric Acid → 2-{(S)-3-[2-((S)-1-Aminoethyl)-6-fluorobenzoimidazol-1-yl]piperidin-1-yl}ethanol

HRID 243038Notes

Reaction equation

HRID 243038 reaction equation
[NH2:1][C@@H:2]([CH3:29])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=1[NH:13][C@H:14]1[CH2:19][CH2:18][CH2:17][N:16]([CH2:20][CH2:21][O:22]C(=O)C(C)(C)C)[CH2:15]1)=O.Cl>>[NH2:1][C@H:2]([C:3]1[N:13]([C@H:14]2[CH2:19][CH2:18][CH2:17][N:16]([CH2:20][CH2:21][OH:22])[CH2:15]2)[C:7]2[CH:8]=[C:9]([F:12])[CH:10]=[CH:11][C:6]=2[N:5]=1)[CH3:29]

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 681573042,2-Dimethylpropionic acid 2-{(S)-3-[2-((S)-2-aminopropionylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl ester

Product 1

HCID 681577312-{(S)-3-[2-((S)-1-Aminoethyl)-6-fluorobenzoimidazol-1-yl]piperidin-1-yl}ethanolYield 47.4%

Procedure

A solution of 2,2-dimethylpropionic acid 2-{(S)-3-[2-((S)-2-aminopropionylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl ester (200 mg, 0.49 mmol), in aqueous 6M HCl (8 mL) was refluxed for 30 min. After cooling to RT the volatiles were removed in vacuo and the resulting residue loaded in dioxane/water (1:1) onto an Isolute® SCX-2 cartridge. The cartridge was washed with dioxane/water (1:1), then dioxane and the product eluted with 10% 880 NH3 in dioxane. The fractions containing product were purified by column chromatography (Si—PCC, gradient 3-18% 2M NH3/MeOH in DCM) affording the title compound as a colourless gum (71.2 mg, 47%). LCMS (Method J): RT 0.39 min [M+H]+ 307.

Workup

  1. customwere removed in vacuo
  2. washThe cartridge was washed with dioxane/water (1:1)
  3. washdioxane and the product eluted with 10% 880 NH3 in dioxane
  4. additionThe fractions containing product
  5. customwere purified by column chromatography (Si—PCC, gradient 3-18% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-86dba2ac00ee4e9a886e8ad7972dc102
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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