Diisopropylethylamine → HCID 58110325, compound

HRID 2068638Notes

Reaction equation

HRID 2068638 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[S:10][CH:9]=[C:8]([C:11]([OH:13])=O)[CH:7]=2)[CH:3]=[N:2]1.[C:14]([O:18][C:19]([N:21]1[CH2:27][CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:14]([O:18][C:19]([N:21]1[CH2:27][CH2:26][CH2:25][N:24]([C:11]([C:8]2[CH:7]=[C:6]([C:4]3[CH:5]=[N:1][NH:2][CH:3]=3)[S:10][CH:9]=2)=[O:13])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581101935-(1H-Pyrazol-4-YL)thiophene-3-carboxylic acid

Product 1

HCID 58110325HCID 58110325, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-(1H-Pyrazol-4-yl)-thiophene-3-carboxylic acid (0.194 g, 1.0 mmol) and [1,4]diazepane-1-carboxylic acid tert-butyl ester (0.25 g, 1.25 mmol) were dissolved in DMF (5 mL) then DIPEA (0.387 g, 3.0 mmol) and HATU (0.46 g, 1.2 mmol) were added and the reaction mixture stirred at room temperature overnight. The solvent was removed by evaporation then the residue was dissolved in DCM and washed with water. The organic phase was washed with 0.5 M HCl then aqueous sodium hydrogen carbonate solution then the organics were evaporated. The crude material was purified by flash chromatography on a 10 g silica II cartridge, eluting with 2% methanol in DCM. The fractions containing the desired product were concentrated under vacuum to give 4-[5-(1H-pyrazol-4-yl)-thiophene-3-carbonyl]-[1,4]diazepane-1-carboxylic acid tert-butyl ester (0.29 g) as a white solid. LCMS m/z 377.32 [M+H]+ R.T.=3.00 min (Analytical Method 6).

Workup

  1. customThe solvent was removed by evaporation
  2. dissolutionthe residue was dissolved in DCM
  3. washwashed with water
  4. washThe organic phase was washed with 0.5 M HCl
  5. customaqueous sodium hydrogen carbonate solution then the organics were evaporated
  6. customThe crude material was purified by flash chromatography on a 10 g silica II cartridge
  7. washeluting with 2% methanol in DCM
  8. additionThe fractions containing the desired product
  9. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-1ce4df66c99b4f478dd49f7f32ca685d
Source dataset
uspto-grants-2012_10
Patent number
US08299063B2

Reaction notes

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