Dichloromethane → HCID 57929885, compound

HRID 1930021Notes

Reaction equation

HRID 1930021 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[CH2:29][CH2:28][CH2:27][N:12]2[C:13]=1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([C:23]([NH2:26])([CH3:25])[CH3:24])=[N:21][N:22]=2)[N:19]=1.C(Cl)Cl.CCN(C(C)C)C(C)C.[CH2:42]1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)[O:44][CH2:43]1>O.C(#N)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[CH2:29][CH2:28][CH2:27][N:12]2[C:13]=1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([C:23]([NH:26][C:43](=[O:44])[CH3:42])([CH3:25])[CH3:24])=[N:21][N:22]=2)[N:19]=1

Participants

7

Reactant 4

HCID 6344Dichloromethane2×HCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 57929857HCID 57929857, compound

Product 1

HCID 57929885HCID 57929885, compoundYield 43.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A flask was charged with 2-(6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)propan-2-amine (0.125 g, 0.316 mmol, prepared using General Procedure I.1 from Example #6, Step B with Example #9, Step A, General Procedure D with hydrazine hydrate, General Procedure E.1 with tert-butyl 2-methyl-1-oxopropan-2-ylcarbamate (prepared using General Procedure A.I.1 from tert-butyl 1-hydroxy-2-methylpropan-2-ylcarbamate), General Procedure Q.1 with HCl) and DCM (2.0 mL) to give a brown solution. To the reaction flask were added DIPEA (0.166 mL, 0.948 mmol) and HOAC (0.022 mL, 0.38 mmol). BOP-Cl (0.161 g, 0.632 mmol, Lancaster) was added in one portion to the solution and the reaction mixture was stirred at ambient temperature for about 90 min. The mixture was poured into DCM (about 30 mL) and washed with 1N HCl (about 30 mL). The aqueous layer and the organic solution was then washed with 5 N HCl (about 2×30 mL). The aqueous solution was basified with 6N NaOH (about 20 mL). The cloudy solution was back-extracted with DCM (2×50 mL). The organic solution was dried over MgSO4, filtered, and the solvent was removed under reduced pressure to give a yellow residue. The product was dissolved into hot ACN (about 4 mL) followed by the addition of water (about 2 mL). The mixture was concentrated under reduced pressure and then lyophilized to give the title compound (0.060 g, 43%): LC/MS (Table 1, Method g) Rt=1.67 min; MS m/z: 474.2 (M+H)+.

Workup

  1. customto give a brown solution
  2. washwashed with 1N HCl (about 30 mL)
  3. washThe aqueous layer and the organic solution was then washed with 5 N HCl (about 2×30 mL)
  4. extractionThe cloudy solution was back-extracted with DCM (2×50 mL)
  5. dry with materialThe organic solution was dried over MgSO4
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customto give a yellow residue
  9. concentrationThe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-2ee246e9831645008ad3d0365b3aad37
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

Loading…