2-Thiopheneacetic acid → HCID 86714377, compound

HRID 1750167Notes

Reaction equation

HRID 1750167 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([OH:9])=O.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[C:29]([O:33][C:34](=[O:58])[C@@H:35]([NH:40][C:41](=[O:57])[C:42]1[CH:47]=[CH:46][C:45]([NH:48][CH:49]([CH:53]([CH3:55])[CH3:54])[CH:50]([CH3:52])[CH3:51])=[C:44]([NH2:56])[CH:43]=1)[CH2:36][CH:37]([CH3:39])[CH3:38])([CH3:32])([CH3:31])[CH3:30]>CN(C=O)C.O.C(Cl)CCl>[C:29]([O:33][C:34](=[O:58])[C@@H:35]([NH:40][C:41](=[O:57])[C:42]1[CH:47]=[CH:46][C:45]([NH:48][CH:49]([CH:50]([CH3:52])[CH3:51])[CH:53]([CH3:54])[CH3:55])=[C:44]([NH:56][C:7](=[O:9])[CH2:6][C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)[CH:43]=1)[CH2:36][CH:37]([CH3:39])[CH3:38])([CH3:30])([CH3:31])[CH3:32]

Participants

8

Reactant 4

HCID 159702-Thiopheneacetic acidHCID 81531Diisopropylethylamine2×HCID 181649HOAtHCID 86714378HCID 86714378, compound

Product 1

HCID 86714377HCID 86714377, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 469 mg of thiophen-2-yl-acetic acid in 7.5 ml of dry DMF 449 mg of HOAT, 633 mg of EDC and 0.75 ml of DIPEA were added at 0° C. After 30 min 1259 mg of (S)-2-[3-Amino-4-(1-isopropyl-2-methyl-propylamino)-benzoylamino]-4-methyl-pentanoic acid tert-butyl ester and 0.75 ml of DIPEA were added and the reaction was stirred at it for 16 h. The reaction was then poured into water and 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 250 mg (15%)) (S)-2-[4-(1-Isopropyl-2-methyl-propylamino)-3-(2-thiophen-2-yl-acetylamino)-benzoylamino]-4-methyl-pentanoic acid tert-butyl ester

Workup

  1. extractionextracted 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-d18a4f3703ab45d89b1221afe6991a86
Source dataset
uspto-grants-2015_10
Patent number
US09156796B2

Reaction notes

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