1,2-Dichloroethane → HCID 90331702, compound

HRID 1752942

Reaction equation

HRID 1752942 reaction equation
[NH2:1][C@H:2]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=2[F:23])=[CH:12][CH:11]=1)[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[P:24]([CH2:28][CH2:29][C:30](O)=[O:31])([OH:27])([OH:26])=[O:25].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:22][C:20]1[CH:19]=[CH:18][C:17]([F:23])=[C:16]([C:13]2[CH:14]=[CH:15][C:10]([CH2:9][C@@H:2]([NH:1][C:30](=[O:31])[CH2:29][CH2:28][P:24](=[O:25])([OH:27])[OH:26])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:11][CH:12]=2)[CH:21]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 16823-Phosphonopropionic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 59607661HCID 59607661, compound

Product 1

HCID 90331702HCID 90331702, compoundYield 11.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R)-ethyl 3-amino-4-(5′-chloro-2′-fluoro-[1,1-biphenyl]-4-yl)butanoate (114 mg, 0.306 mmol), 3-phosphonoproprionic acid (47.2 mg, 0.306 mmol), EDC (58.7 mg, 0.306 mmol) and HOBT (46.9 mg, 0.306 mmol) were mostly dissolved in DMF (1 mL), and DIPEA (0.321 mL, 1.837 mmol) was added. The reaction mixture was stirred and heated at 70° C. approximately 18 hours, then filtered and purified by HPLC: 30-80% ACN/H2O 0.1% TFA, 40 mL/min over 15 min 30×100 Sunfire C18, product elutes approximately 5.5-8 min. A mixed fraction was repurified on a 20-55% gradient over 20 min, and product eluted ˜12.5-13 min. The fractions were evaporated to dryness to afford (R)-(3-((1-(5′-chloro-2′-fluoro-[1,1-biphenyl]-4-yl)-4-ethoxy-4-oxobutan-2-yl)amino)-3-oxopropyl)phosphonic acid (17 mg) LCMS (ES+) C21H24ClFNO6P: Calc.: 471.1; Found: 472.0[M+H]+.

Workup

  1. temperatureheated at 70° C. approximately 18 hours
  2. filtrationfiltered
  3. custompurified by HPLC
  4. customA mixed fraction was repurified on a 20-55% gradient over 20 min
  5. washproduct eluted ˜12.5-13 min
  6. customThe fractions were evaporated to dryness

Sources & evidence

ORD record
ord-0bb2365961004c3b8ad64fa1862f09ee
Source dataset
uspto-grants-2015_10
Patent number
US09163040B2

Linked notes

Loading…