Diisopropylethylamine → HCID 71294340, compound

HRID 240745Notes

Reaction equation

HRID 240745 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:15]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[N:16][CH:17]=[C:18]([C:20](O)=[O:21])[CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N:30](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.N=[C:61]1[CH2:66][CH:65]([CH2:67][CH2:68][OH:69])[CH2:64][CH2:63][NH:62]1>CN(C=O)C.O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[C:15]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[N:16][CH:17]=[C:18]([C:20](=[O:21])[NH:30][N:62]3[CH2:63][CH2:64][CH:65]([CH2:67][CH2:68][OH:69])[CH2:66][CH2:61]3)[CH:19]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 71294354HCID 71294354, compoundHCID 178507633HCID 178507633, compound

Product 1

HCID 71294340HCID 71294340, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a 10 mL round-bottomed flask, the above prepared 2-(2,2,2-trifluoro-ethoxy)-3′,4′,5′,6′-tetrahydro-2′H-[3,4′]bipyridinyl-5,1′-dicarboxylic acid 1′-tert-butyl ester (100 mg, 247 mmol, Eq: 1.00) was combined with tetrahydrofuran (3 mL) and DMF (1 mL) to give a colorless solution. TBTU (119 mg, 371 μmol, Eq: 1.5) and N,N-diisopropylethylamine (160 mg, 216 μl, 1.24 mmol, Eq: 5) were added and the reaction mixture was stirred for 10 min at rt before 2-(1-aminopiperidin-4-yl)ethanol (61.1 mg, 297 μmol, Eq: 1.2, preparation see Example 38) was added and the reaction mixture kept overnight at rt. The reaction mixture was then quenched with sat NH4Cl sol. 10 mL and extracted with EtOAc (2×20 mL). The organic layers were washed with 1 M NaOH, then with H2O/NaCl sol., combined, dried over Na2SO4, and concentrated in vacuo. Purification by flash chromatography (silica gel, 20 g, 2% to 5% MeOH in DCM) delivered eventually 101 mg of the title compound as white foam; MS (EI) 531.6 (M+H)+.

Workup

  1. customto give a colorless solution
  2. additionwas added
  3. customThe reaction mixture was then quenched with sat NH4Cl sol. 10 mL
  4. extractionextracted with EtOAc (2×20 mL)
  5. washThe organic layers were washed with 1 M NaOH
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography (silica gel, 20 g, 2% to 5% MeOH in DCM)

Sources & evidence

ORD record
ord-c2e42df383ff424ba2e28baa1e7dbbfc
Source dataset
uspto-grants-2014_02
Patent number
US08648099B2

Reaction notes

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