1-(Phenylmethyl) butanedioate → HCID 59607643, compound

HRID 70832Notes

Reaction equation

HRID 70832 reaction equation
[CH2:1]([O:8][C:9](=[O:15])[CH2:10][CH2:11][C:12]([OH:14])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1.[NH2:37][C@H:38]([CH2:43][C:44]1[CH:49]=[CH:48][C:47]([C:50]2[CH:55]=[CH:54][CH:53]=[C:52]([Cl:56])[CH:51]=2)=[CH:46][CH:45]=1)[CH2:39][C:40]([OH:42])=[O:41].CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH2:1]([O:8][C:9](=[O:15])[CH2:10][CH2:11][C:12]([NH:37][C@H:38]([CH2:43][C:44]1[CH:49]=[CH:48][C:47]([C:50]2[CH:55]=[CH:54][CH:53]=[C:52]([Cl:56])[CH:51]=2)=[CH:46][CH:45]=1)[CH2:39][C:40]([OH:42])=[O:41])=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 87881-(Phenylmethyl) butanedioateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 59607726HCID 59607726, compound

Product 1

HCID 59607643HCID 59607643, compoundYield 38.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Procedure

A solution of succinic acid mono-benzyl ester (71.1 mg, 0.342 mmol), EDCI (65.5 mg, 0.342 mmol) and HOAt (46.5 mg, 0.342 mmol) in DMF (1 ml), which is allowed to stir at room temperature for 1 hour, is added to a solution of (R)-3-amino-4-(3′-chlorobiphenyl-4-yl)butanoic acid (66 mg, 0.228 mmol) and DIPEA (0.080 ml, 0.456 mmol) in a mixed solvent DMF (2 ml) and water (2 ml). The reaction mixture is allowed to stir for 3 hours, and then diluted with H2O. The products are extracted twice with EtOAc. The combined organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated to give crude. The resulting residue is purified by preparative HPLC using a gradient of 20% MeCN/water (0.1% TFA) to 100% MeCN to give (R)-3-(4-(benzyloxy)-4-oxobutanamido)-4-(3′-chlorobiphenyl-4-yl)butanoic acid (42.4 mg) as a white solid; HPLC retention time=1.22 minutes (condition B); MS (m+1)=480.35; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.44-2.75 (m, 6 H) 2.86-2.99 (m, 2 H) 4.48-4.56 (m, 1 H) 5.11 (s, 2 H) 6.29 (br d, J=8.6 Hz, 1 H) 6.97-7.07 (m, 10 H) 7.25-7.36 (m, 2 H) 7.42-7.50 (m, 2 H) 7.54 (br t, J=1.6 Hz, 1 H).

Workup

  1. stirringto stir for 3 hours
  2. extractionThe products are extracted twice with EtOAc
  3. washThe combined organic layer is washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give crude
  8. customThe resulting residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-a2c9eb35e7114443bb499e397de97da1
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

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