Borane → HCID 86669701, compound

HRID 1623964Notes

Reaction equation

HRID 1623964 reaction equation
[CH:1]1([C@H:4]([NH:8][C:9]([C:11]2[C:12]3[CH2:13][C@H:14]4[CH2:27][C@H:15]4[C:16]=3[N:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])[N:18]=2)=[O:10])[C:5](O)=[O:6])[CH2:3][CH2:2]1.B.C([O-])(O)=O.[Na+]>C1COCC1>[CH:1]1([C@H:4]([NH:8][C:9]([C:11]2[C:12]3[CH2:13][C@H:14]4[CH2:27][C@H:15]4[C:16]=3[N:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])[N:18]=2)=[O:10])[CH2:5][OH:6])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6331BoraneHCID 516892Sodium BicarbonateHCID 68182443HCID 68182443, compound

Product 1

HCID 86669701HCID 86669701, compoundYield 42.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
23 °C

Procedure

To a solution of (S)-cyclopropyl-{[(1aR,5aR)-2-(2,4-difluoro-phenyl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carbonyl]-amino}-acetic acid (175 mg, 0.469 mmol) in THF (4 mL) was added a 1.0 M THF solution of borane (1.875 mL, 1.875 mmol). The reaction was stirred at 23° C. for 2.5 h. Saturated aqueous NaHCO3 (25 mL) was added. The mixture was extracted with dichloromethane (3×25 mL). The combined organic extracts were dried (MgSO4), filtered, then concentrated. The residue was purified by silica gel column chromatography followed by reversed-phase prep HPLC to give the title compound as a white solid (72 mg). LCMS m/z=360.4 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 0.35-0.42 (m, 2H), 0.48 (td, J=4.6, 3.4 Hz, 1H), 0.52-0.64 (m, 2H), 0.94-1.03 (m, 1H), 1.15 (td, J=7.8, 4.9 Hz, 1H), 2.09-2.14 (m, 1H), 2.24-2.31 (m, 1H), 2.94 (d, J=16.6 Hz, 1H), 3.05 (dd, J=16.6, 6.3 Hz, 1H), 3.18 (bs, 1H), 3.27-3.34 (m, 1H), 3.78-3.80 (m, 1H), 3.90 (dd, J=11.1, 3.0 Hz, 1H), 7.00-7.05 (m, 2H), 7.09 (d, J=6.4 Hz, 1H), 7.62-7.68 (m, 1H).

Workup

  1. extractionThe mixture was extracted with dichloromethane (3×25 mL)
  2. dry with materialThe combined organic extracts were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5e3c172860e542809f84a9f6bc0b5422
Source dataset
uspto-grants-2014_07
Patent number
US08778950B2

Reaction notes

Loading…