Diisopropylethylamine → 5-Cyclopropyl-6-cyclopropylmethoxy-pyrazine-2-carboxylic acid ((S)-carbamoyl-phenyl-methyl)-amide

HRID 1477779

Reaction equation

HRID 1477779 reaction equation
[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([C:15]([OH:17])=O)=[N:8][C:9]=2[O:10][CH2:11][CH:12]2[CH2:14][CH2:13]2)[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:49][C@@H:50]([C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)[C:51]([NH2:53])=[O:52]>CN(C=O)C>[C:51]([C@@H:50]([NH:49][C:15]([C:7]1[CH:6]=[N:5][C:4]([CH:1]2[CH2:2][CH2:3]2)=[C:9]([O:10][CH2:11][CH:12]2[CH2:13][CH2:14]2)[N:8]=1)=[O:17])[C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1)(=[O:52])[NH2:53]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 729986(S)-(+)-2-Phenylglycine amideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 866823315-Cyclopropyl-6-cyclopropylmethoxy-pyrazine-2-carboxylic acid

Product 1

HCID 715255765-Cyclopropyl-6-cyclopropylmethoxy-pyrazine-2-carboxylic acid ((S)-carbamoyl-phenyl-methyl)-amideYield 9.58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Cyclopropyl-6-cyclopropylmethoxy-pyrazine-2-carboxylic acid (Example 10 g, 100 mg, 0.43 mmol) was suspended in DMF (3 mL). TBTU (224.14 mg, 0.85 mmol), DIEA (0.31 mL, 2.24 mmol) and (αS)-α-amino-benzeneacetamide (CAN 6485-52-5, 51.2 mg, 0.51 mmol) were added and the reaction mixture was stirred at room temperature for 12 hours. The mixture was extracted with ethyl acetate and water; the organic phase was dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by reverse phase preparative HPLC (Xbridge-C18, 5 μ, 19×250 mm/acetonitrile/0.1% ammonia in water) to give the desired product (15 mg, 9.58%) as white solid; LC-MS (UV peak area, ESI) 93.20%, 367.4 (M+H).

Workup

  1. extractionThe mixture was extracted with ethyl acetate and water
  2. dry with materialthe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by reverse phase preparative HPLC (Xbridge-C18, 5 μ, 19×250 mm/acetonitrile/0.1% ammonia in water)

Sources & evidence

ORD record
ord-45669c99ab514df781379e6c3717cfaa
Source dataset
uspto-grants-2016_08
Patent number
US09403808B2

Linked notes

Loading…