Azepane → 4-[4-(Azepane-1-carbonyl)-thiophen-2-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 1809100Notes

Reaction equation

HRID 1809100 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[S:15][CH:16]=[C:17]([C:19]([OH:21])=O)[CH:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[NH:29]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[S:15][CH:16]=[C:17]([C:19]([N:29]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)=[O:21])[CH:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 8119AzepaneHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595425244-(4-Carboxy-thiophen-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Product 1

HCID 595424584-[4-(Azepane-1-carbonyl)-thiophen-2-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl esterYield 69.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

4-(4-Carboxy-thiophen-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.1 g, 0.35 mmol) was dissolved in DMF (2 mL) and triethylamine (1.0 mmol). Homopiperidine (1.4 mmol) was added with HATU (0.35 mmol) and the mixture stirred for 2 hours. The mixture was diluted with DCM (20 mL) and washed with water. The organic solution was separated, dried with anhydrous magnesium sulphate, filtered and evaporated. The residue was then purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid) over 30 minutes. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.095 g). LCMS m/z 391.56 [M+H]+ RT=4.09min (Analytical Method 4).

Workup

  1. washwashed with water
  2. customThe organic solution was separated
  3. dry with materialdried with anhydrous magnesium sulphate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was then purified by HPLC
  7. washeluting with 10%-98% acetonitrile in water (0.1% formic acid) over 30 minutes
  8. additionThe fractions containing the desired product
  9. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-9b0407b7e65445d592b8ebdde9292166
Source dataset
uspto-grants-2013_01
Patent number
US08362008B2

Reaction notes

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