Hydrochloric Acid → HCID 86714383, compound

HRID 1750171Notes

Reaction equation

HRID 1750171 reaction equation
[CH2:1]([CH:3]([N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]([NH:17][C@@H:18]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:19](O)=[O:20])=[O:16])=[CH:14][C:9]=2[N:8]=[C:7]1[CH2:26][C:27]1[S:28][CH:29]=[CH:30][CH:31]=1)[CH2:4][CH3:5])[CH3:2].C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[C:52]([O:56][C:57](=[O:60])[CH2:58][NH2:59])([CH3:55])([CH3:54])[CH3:53].Cl>CN(C=O)C.O.C(Cl)CCl>[C:52]([O:56][C:57](=[O:60])[CH2:58][NH:59][C:19](=[O:20])[C@@H:18]([NH:17][C:15]([C:13]1[CH:12]=[CH:11][C:10]2[N:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[C:7]([CH2:26][C:27]3[S:28][CH:29]=[CH:30][CH:31]=3)=[N:8][C:9]=2[CH:14]=1)=[O:16])[CH2:22][CH:23]([CH3:24])[CH3:25])([CH3:55])([CH3:54])[CH3:53]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531Diisopropylethylamine2×HCID 181649HOAtHCID 2725036Glycine tert-butyl ester hydrochlorideHCID 73442765HCID 73442765, compound

Product 1

HCID 86714383HCID 86714383, compoundYield 32.2%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 100 mg of (S)-2-{[1-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carbonyl]-amino}-4-methyl-pentanoic acid in 1 ml of dry DMF 12 mg of HOAT, 41 mg of EDC and 0.13 ml of DIPEA were added at 0° C. After 15 min 30 mg of glycine tert.-butylester-hydrochloride and 0.03 ml of DIPEA were added and the reaction was stirred at it for 16 h. The reaction was then poured into water and the pH was adjusted to 3 by the addition of 2 M aqueous hydrochloric acid. The reaction was extracted with ethyl acetate three times. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulphate and concentrated. The crude product was purified by HPLC to yield 32 mg (32%) of ((S)-2-{[1-(1-ethyl-propyl)-2-thiophen-2-ylmethyl-1H-benzoimidazole-5-carbonyl]-amino}-4-methyl-pentanoylamino)-acetic acid tert.-butyl ester.

Workup

  1. extractionThe reaction was extracted with ethyl acetate three times
  2. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated
  5. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-13ff153db8f64652ac0b0afebc85ef4a
Source dataset
uspto-grants-2015_10
Patent number
US09156796B2

Reaction notes

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