Triethylamine → HCID 68168672, compound

HRID 716677Notes

Reaction equation

HRID 716677 reaction equation
[CH3:1][C:2]1[S:6][C:5]2[NH:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[N:14]=[C:15]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[C:4]=2[CH:3]=1.C(N(CC)CC)C.Cl[C:31]([O:33][CH2:34][Cl:35])=[O:32]>ClCCl>[CH3:1][C:2]1[S:6][C:5]2=[N:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[N:14]([C:31]([O:33][CH2:34][Cl:35])=[O:32])[C:15]([N:16]3[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]3)=[C:4]2[CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62754Chloromethyl chloroformateHCID 135398745Olanzapine

Product 1

HCID 68168672HCID 68168672, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of olanzapine (18.0 g, 57.7 mmol) and triethylamine (16 mL, 0.12 mol) in dichloromethane (250 mL) was warmed to 35° C. and once a clear solution formed, the reaction was cooled to 5° C. To this was added chloromethyl chloroformate (7.6 mL, 86.5 mmol) over 20 minutes. The reaction was stirred at room temperature for 30 min and allowed to warm to room temperature. After 15 min at room temperature the reaction mixture was diluted with dichloromethane (100 mL), then washed with aq satd NaHCO3 (75 mL) and water (350 mL). The organic phase was dried over MgSO4 and filtered. The organic phase was then concentrated under vacuum at 45° C. to a volume of −150 mL. The mixture was diluted with ethyl acetate (30 mL) and ˜20-30 mL further was evaporated under vacuum. The mixture was cooled to room temperature and the resulting solid precipitate filtered and washed with ethyl acetate. After drying under vacuum at 35° C. for 90 min chloromethyl 2-methyl-4-(4-methylpiperazin-1-yl)-5H-benzo[b]thieno[2,3-e][1,4]diazepine-5-carboxylate [A] (17.1 g, 73%) was obtained as a yellow solid. 1H-NMR (300 MHz, CDCl3) δ 7.62-7.14 (4H, m), 6.27-6.22 (1H, m), 5.84-5.69 (1H, m), 5.47-5.23 (1H, m), 3.89-3.63 (4H, m), 2.66-2.22 (10H, m).

Workup

  1. customonce a clear solution formed
  2. temperatureto warm to room temperature
  3. washwashed with aq satd NaHCO3 (75 mL) and water (350 mL)
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationThe organic phase was then concentrated under vacuum at 45° C. to a volume of −150 mL
  7. additionThe mixture was diluted with ethyl acetate (30 mL) and ˜20-30 mL
  8. customfurther was evaporated under vacuum
  9. temperatureThe mixture was cooled to room temperature
  10. filtrationthe resulting solid precipitate filtered
  11. washwashed with ethyl acetate
  12. dry with materialAfter drying under vacuum at 35° C. for 90 min chloromethyl 2-methyl-4-(4-methylpiperazin-1-yl)-5H-benzo[b]thieno[2,3-e][1,4]diazepine-5-carboxylate [A] (17.1 g, 73%)
  13. customwas obtained as a yellow solid

Sources & evidence

ORD record
ord-89fc145879a84aefbbeaa014a3254fec
Source dataset
uspto-grants-2015_11
Patent number
US09193685B2

Reaction notes

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