Pyridine → HCID 67443215, compound

HRID 1400876Notes

Reaction equation

HRID 1400876 reaction equation
[NH2:1][C:2]1[CH:36]=[CH:35][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[CH:17]=[N:18][N:19]([CH2:21][CH2:22][N:23]([CH2:31][CH2:32][O:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:20]=4)[S:15][C:8]=23)=[C:4]([F:37])[CH:3]=1.[N:38]1[CH:43]=[CH:42][CH:41]=C[CH:39]=1.ClC(OC1C=CC=CC=1)=[O:46].C1(N)CC1>CN(C=O)C>[CH:43]1([NH:38][C:39](=[O:46])[NH:1][C:2]2[CH:36]=[CH:35][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]4[CH:13]=[C:14]([C:16]5[CH:17]=[N:18][N:19]([CH2:21][CH2:22][N:23]([CH2:31][CH2:32][O:33][CH3:34])[C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:29])[CH3:27])[CH:20]=5)[S:15][C:8]=34)=[C:4]([F:37])[CH:3]=2)[CH2:41][CH2:42]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 57919630HCID 57919630, compound

Product 1

HCID 67443215HCID 67443215, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of tert-butyl 2-(4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1H-pyrazol-1-yl)ethyl(2-methoxyethyl)carbamate (245, 1.22 g, 2.312 mmol) and pyridine (374 μL, 4.62 mmol) in DMF (30 mL) at 0° C. was added phenyl chloroformate (348 μl, 2.77 mmol) and the reaction mixture was stirred for 30 min. Cyclopropylamine (407 μl, 5.78 mmol) was added at 0° C. and the reaction mixture was heated at 60° C. for an additional 30 min. After cooling to RT, the reaction mixture was quenched by addition of water and a saturated solution of ammonium chloride, and extracted with AcOEt. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 80 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV). The desired fractions were collected and concentrated to afford the title compound 246 (722 mg, 0.18 mmol, 61% yield) as a yellow solid. MS (m/z): 611.63 (M+H).

Workup

  1. temperatureAfter cooling to RT
  2. customthe reaction mixture was quenched by addition of water
  3. extractiona saturated solution of ammonium chloride, and extracted with AcOEt
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by Biotage (SNAP 80 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV)
  10. customThe desired fractions were collected
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-90eaa5e726a14e74b90977fc0bde1f55
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

Loading…