Pyridine → HCID 67441318, compound

HRID 1400883Notes

Reaction equation

HRID 1400883 reaction equation
[CH2:1]([O:3][CH:4]([O:29][CH2:30][CH3:31])[CH2:5][N:6]1[CH:10]=[C:9]([C:11]2[S:19][C:18]3[C:13](=[N:14][CH:15]=[CH:16][C:17]=3[O:20][C:21]3[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][C:22]=3[F:28])[CH:12]=2)[N:8]=[CH:7]1)[CH3:2].[N:32]1[CH:37]=[CH:36][CH:35]=C[CH:33]=1.ClC(OC1C=CC=CC=1)=[O:40].C1(N)CC1>CN(C=O)C>[CH:37]1([NH:32][C:33]([NH:25][C:24]2[CH:26]=[CH:27][C:21]([O:20][C:17]3[CH:16]=[CH:15][N:14]=[C:13]4[CH:12]=[C:11]([C:9]5[N:8]=[CH:7][N:6]([CH2:5][CH:4]([O:3][CH2:1][CH3:2])[O:29][CH2:30][CH3:31])[CH:10]=5)[S:19][C:18]=34)=[C:22]([F:28])[CH:23]=2)=[O:40])[CH2:35][CH2:36]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828Cyclopropylamine2×HCID 67441620HCID 67441620, compound

Product 1

HCID 67441318HCID 67441318, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of amine 262 (2.86 g, 6.46 mmol) and pyridine (1.04 mL, 12.93 mmol) in DMF (50 mL) at 0° C. was added phenyl chloroformate (973 μl, 7.76 mmol). After 30 min, cyclopropylamine (1.14 mL, 16.16 mmol) was added at 0° C. and the reaction mixture was heated at 60° C. for 45 min. More cyclopropylamine (1 mL, 14.18 mmol) was added and the reaction mixture was heated at 60° C. for an additional 10 min. After cooling to RT, the reaction mixture was quenched by addition of water to form a precipitate. The solid was collected by filtration, washed with water and dried under vacuum for 2 h. 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, concentrated, triturated with MTBE and dried under high vacuum to afford the title compound 263 (2.95 g, 5.61 mmol, 87% yield) as a pink solid. MS (m/z): 526.60 (M+H).

Workup

  1. temperaturethe reaction mixture was heated at 60° C. for an additional 10 min
  2. temperatureAfter cooling to RT
  3. customthe reaction mixture was quenched by addition of water
  4. customto form a precipitate
  5. filtrationThe solid was collected by filtration
  6. washwashed with water
  7. customdried under vacuum for 2 h
  8. customThe residue was purified by Biotage (SNAP 80 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV)
  9. customThe desired fractions were collected
  10. concentrationconcentrated
  11. customtriturated with MTBE
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-a0eb392747154663be5eec52800deb4e
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

Loading…