Dimethylformamide → HCID 68864904, compound

HRID 1985795Notes

Reaction equation

HRID 1985795 reaction equation
C1(CS([CH2:8][C@H:9]([NH:13][C@@H:14]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:15]([F:18])([F:17])[F:16])[C:10]([OH:12])=O)(=O)=O)CC1.C1([CH2:28][S:29](C[C@H](N[C@H](C2C=CC=CC=2)C(F)(F)F)C(O)=O)(=[O:31])=[O:30])CC1.Cl.[NH2:50][C:51]1([C:54]#[N:55])[CH2:53][CH2:52]1.CN1[CH2:62][CH2:61]OCC1.[CH3:63]N(C=O)C>>[C:54]([C:51]1([NH:50][C:10](=[O:12])[C@@:9]([S:29]([CH3:28])(=[O:31])=[O:30])([NH:13][C@@H:14]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:15]([F:16])([F:17])[F:18])[CH2:8][CH:62]2[CH2:61][CH2:63]2)[CH2:53][CH2:52]1)#[N:55]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 145863631-Amino-1-cyclopropanecarbonitrile hydrochlorideHCID 68863829HCID 68863829, compoundHCID 68865558HCID 68865558, compound

Product 1

HCID 68864904HCID 68864904, compound

Procedure

A solution of 3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-phenylethylamino)-propionic acid and 3-cyclopropylmethanesulfonyl-2(R)-(2,2,2-trifluoro-1(R)-phenylethylamino)-propionic acid (140 mg, 0.38 mmol), 1-aminocyclopropane-carbonitrile hydrochloride (45 mg, 0.38 mmol) HATU (173 mg, 0.46 mmol) and N-methylmorpholine (100 μL, 0.91 mmol) in anhydrous DMF (0.75 mL) was stirred at room temperature for 16 h. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The aqueous layer with extracted again with ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by silica gel chromatography using 1:1 hexanes: ethyl acetate to give a fraction that was further purified by crystallization from diethyl ether and hexanes to give N-(1-cyanocyclopropyl)-3-cyclopropyl-methanesulfonyl-2(R)-(2,2,2-trifluoro-1(S)-phenylethylamino)propionamide (6.77 mg).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  2. extractionThe aqueous layer with extracted again with ethyl acetate
  3. washThe combined ethyl acetate layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel chromatography
  7. customethyl acetate to give a fraction that
  8. customwas further purified by crystallization from diethyl ether and hexanes

Sources & evidence

ORD record
ord-2e814ebd9a564f5682bf2ea9c5b7c636
Source dataset
uspto-grants-2009_06
Patent number
US07547701B2

Reaction notes

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