Hydrochloric Acid → (1aS,5aS)-2-(4-Chloro-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic Acid (2-Fluoro-1-hydroxymethyl-2-methyl-propyl)-amide

HRID 1624007Notes

Reaction equation

HRID 1624007 reaction equation
C[O:2][C:3](=O)[CH:4]([NH:9][C:10]([C:12]1[C:13]2[CH2:14][C@@H:15]3[CH2:27][C@@H:16]3[C:17]=2[N:18]([C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][N:21]=2)[N:19]=1)=[O:11])[C:5]([F:8])([CH3:7])[CH3:6].[BH4-].[Na+].Cl>O1CCOCC1.O>[F:8][C:5]([CH3:7])([CH3:6])[CH:4]([NH:9][C:10]([C:12]1[C:13]2[CH2:14][C@@H:15]3[CH2:27][C@@H:16]3[C:17]=2[N:18]([C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][N:21]=2)[N:19]=1)=[O:11])[CH2:3][OH:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 681823882-{[(1aS,5aS)-2-(4-Chloro-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carbonyl]-amino}-3-fluoro-3-methyl-butyric Acid Methyl Ester

Product 1

HCID 86669712(1aS,5aS)-2-(4-Chloro-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic Acid (2-Fluoro-1-hydroxymethyl-2-methyl-propyl)-amide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

2-{[(1aS,5aS)-2-(4-Chloro-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carbonyl]-amino}-3-fluoro-3-methyl-butyric acid methyl ester (171 mg, 0.420 mmol) was dissolved in dioxane (3 mL) and water (2 mL). Sodium borohydride (63.6 mg, 1.681 mmol) was added slowly at 0° C. The reaction mixture was stirred at room temperature overnight, neutralized with 1 N HCl solution, then extracted with ethyl acetate. The combined organics were washed with water, dried over anhydrous Na2SO4, filtered then concentrated. The residue was purified by column chromatography to give the title compound as a white foam. LCMS m/z=379.4 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 0.45-0.50 (m, 1H), 1.23-1.30 (m, 1H), 1.47 (d, J=22.1 Hz, 3H), 1.53 (d, J=21.7 Hz, 3H), 2.22-2.30 (m, 1H), 2.33-2.40 (m, 1H), 2.78-2.85 (m, 1H), 2.88-3.05 (m, 2H), 3.90-4.00 (m, 2H), 4.11-4.25 (m, 1H), 7.22 (dd, J=5.3 and 1.8 Hz, 1H), 7.36 (d, J=9.3 Hz, 1H), 7.97 (d, J=1.4 Hz, 1H), 8.35 (d, J=5.3 Hz, 1H).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organics were washed with water
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationthen concentrated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-41102acc839e40c9bcb78a1368ba1185
Source dataset
uspto-grants-2014_07
Patent number
US08778950B2

Reaction notes

Loading…