Diisopropylethylamine → HCID 58748209, compound

HRID 1162618Notes

Reaction equation

HRID 1162618 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][CH:10]2[CH2:15][CH2:14][CH2:13][N:12]([CH2:16][C:17]([OH:19])=O)[CH2:11]2)=[O:8])=[CH:4][CH:3]=1.C(N(C(C)C)C(C)C)C.[NH2:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]2=[O:42])=[CH:32][C:31]=1[F:43].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1>C(#N)C.CN(C=O)C>[F:43][C:31]1[CH:32]=[C:33]([N:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]2=[O:42])[CH:34]=[CH:35][C:30]=1[NH:29][C:17]([CH2:16][N:12]1[CH2:13][CH2:14][CH2:15][CH:10]([NH:9][C:7]([C:5]2[S:6][C:2]([Cl:1])=[CH:3][CH:4]=2)=[O:8])[CH2:11]1)=[O:19]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 221815481-(4-Amino-3-fluorophenyl)pyridin-2-oneHCID 58748275HCID 58748275, compound

Product 1

HCID 58748209HCID 58748209, compoundYield 23.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

9.3 To a stirred suspension of 300 mg {3-[(5-chloro-thiophene-2-carbonyl)-amino]-piperidin-1-yl}-acetic acid (containing 2 mol equivalents of sodium chloride) at r.t. in 5 ml acetonitrile and 0.5 ml DMF under an argon atmosphere were added 0.5 ml N-ethyldiisopropylamine, 175 mg 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one (CAS 536747-52-1, prepared according to WO 2003045912) and 365 mg BOP-Cl. The compact slurry was then stirred at r.t. for 18 h. The mixture was concentrated. The residue was taken up with CH2Cl2, washed with 1 N NaOH, H2O and brine, dried (MgSO4), filtered and concentrated. The crude product was purified by chromatography (silica gel; gradient: cyclohexane to EtOAc) to give 98 mg 5-chloro-thiophene-2-carboxylic acid (1-{[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-methyl}-piperidin-3-yl)-amide. White solid. MS 489.5 ([M+H]+)

Workup

  1. concentrationThe mixture was concentrated
  2. washwashed with 1 N NaOH, H2O and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by chromatography (silica gel; gradient: cyclohexane to EtOAc)

Sources & evidence

ORD record
ord-bffee0065b7c4b2bb4b1f01836d6ac67
Source dataset
uspto-grants-2010_10
Patent number
US07820699B2

Reaction notes

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