Water → HCID 57669522, compound

HRID 2174353Notes

Reaction equation

HRID 2174353 reaction equation
[N:1]1[NH:2][N:3]=[N:4][C:5]=1[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([OH:23])=O.C[O:25][C:26]([O:29]C)([CH3:28])C.Cl.CN(C)[CH2:34][CH2:35][CH2:36]N=C=NCC.[OH:43][C:44]1[C:52]2[N:51]=NN[C:48]=2C=CC=1.[CH:53](NC(C)C)(C)C.[OH2:60]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:35]([O:60][C:44](=[O:43])[CH:52]([NH:51][C:21](=[O:23])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][C:5]1[N:1]=[N:2][NH:3][N:4]=1)[CH2:48][CH2:28][C:26]([OH:25])=[O:29])([CH3:36])([CH3:53])[CH3:34]

Participants

9

Reactant 6

HCID 962WaterHCID 64952,2-DimethoxypropaneHCID 7912DiisopropylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5766953816-(2H-Tetrazol-5-yl)hexadecanoic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 57669522HCID 57669522, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

16-(2H-Tetrazol-5-yl)hexadecanoic acid (433 mg, 1.34 mmol) was heated in toluene (5 mL) and 2,2-dimethoxypropane (2 mL, 16 mmol) to reflux for to minutes. The solvent was removed in vacuo. Ethyl acetate (10 mL) was added, followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (359 mg, 1.87 mmol) and 1 hydroxybenzotriazol (281 mg, 2 mmol). The reaction was stirred at room temperature for 30 min, and a mixture of L-glutamic acid alpha tert-butyl-gamma benzyl diester hydrochloride (661 mg, 2 mmol), diisopropylamin (0.34 mL, 2 mmol), and ethyl acetate (4 mL) was added. The mixture was stirred at room temperature overnight. The reaction was distributed between ethyl acetate (50 mL) and water (50 mL). The organic phase was dried (Na2SO4) and the solvent removed in vacuo. The crude 2-(16-2H-tetrazol-5-yl-hexadecanoylamino)pentanedioic acid 5-benzyl ester 1-tert-butyl ester was purified on C-18 RP-HPLC 5 cm×20 cm, flow 20 ml/min using a acetonitrile/water 60-90% gradient containing 0.1% TFA. Fractions containing 2-(16-2H-tetrazol-5-yl-hexadecanoylamino)pentanedioic acid 5-benzyl ester 1-tert-butyl ester were collected and the solvent removed in vacuo. The residue was redissolved in ethyl acetate (10 mL), palladium on activated charcoal (200 mg) was added, and the mixture was stirred under a hydrogen atmosphere (1 atm) for 3 hours. The mixture was filtered and the solvent removed in vacou to yield 2-(16-2H-tetrazol-5-yl-hexadecanoylamino)pentanedioic acid 1-tert-butyl ester (100 mg).

Workup

  1. customThe solvent was removed in vacuo
  2. additionEthyl acetate (10 mL) was added
  3. additionwas added
  4. stirringThe mixture was stirred at room temperature overnight
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. customthe solvent removed in vacuo
  7. customThe crude 2-(16-2H-tetrazol-5-yl-hexadecanoylamino)pentanedioic acid 5-benzyl ester 1-tert-butyl ester was purified on C-18 RP-HPLC 5 cm×20 cm
  8. additiongradient containing 0.1% TFA
  9. additionFractions containing 2-(16-2H-tetrazol-5-yl-hexadecanoylamino)pentanedioic acid 5-benzyl ester 1-tert-butyl ester
  10. customwere collected
  11. customthe solvent removed in vacuo
  12. dissolutionThe residue was redissolved in ethyl acetate (10 mL)
  13. additionpalladium on activated charcoal (200 mg) was added
  14. stirringthe mixture was stirred under a hydrogen atmosphere (1 atm) for 3 hours
  15. filtrationThe mixture was filtered
  16. customthe solvent removed in vacou

Sources & evidence

ORD record
ord-d5ab470fa4624d0cb9d989debdb94ac6
Source dataset
uspto-grants-2015_06
Patent number
US09061067B2

Reaction notes

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