Triethylamine → HCID 66585128, compound

HRID 2167412Notes

Reaction equation

HRID 2167412 reaction equation
[CH3:1][C@@H:2]1[NH:8][CH2:7][CH2:6][CH2:5][N:4]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3]1.C(N(CC)CC)C.Cl.[F:24][C:25]1[C:34]2[C:33]([S:35](Cl)(=[O:37])=[O:36])=[CH:32][CH:31]=[CH:30][C:29]=2[CH:28]=[N:27][CH:26]=1>C(#N)C>[F:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][C:33]=2[S:35]([N:8]2[CH2:7][CH2:6][CH2:5][N:4]([C:9]([O:11][C:12]([CH3:14])([CH3:13])[CH3:15])=[O:10])[CH2:3][C@@H:2]2[CH3:1])(=[O:36])=[O:37])[CH:28]=[N:27][CH:26]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 29981001(S)-1-Boc-2-methyl-[1,4]diazepaneHCID 86686407HCID 86686407, compound

Product 1

HCID 66585128HCID 66585128, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (S)-tert-butyl 3-methyl-1,4-diazepane-1-carboxylate (2.76 kg, 12.9 mol) and triethylamine (2.97 kg, 29.3 mol) in acetonitrile (45.2 kg) was added 4-fluoroisoquinoline-5-sulfonyl chloride hydrochloride (3.30 kg, 11.7 mol) and washed well with acetonitrile (6.45 kg) while ice cooling under an argon atmosphere. The resulting mixture was stirred for two hours while ice cooling. After confirming the disappearance of the starting materials by high-performance liquid chromatography (HPLC), the reaction mixture was concentrated under reduced pressure. To the residue were added ethyl acetate (74.3 kg) and a 5% sodium bicarbonate solution (66.0 kg) for extraction. The resulting organic layer was washed with water (66.0 kg) and a 20% aqueous solution of sodium chloride (33.0 kg), and then dried over anhydrous sodium sulfate. The solvent was then evaporated under reduced pressure to give the target product as a yellow amorphous product (5.18 kg, quantitative).

Workup

  1. washwashed well with acetonitrile (6.45 kg) while ice cooling under an argon atmosphere
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. additionTo the residue were added ethyl acetate (74.3 kg)
  4. extractiona 5% sodium bicarbonate solution (66.0 kg) for extraction
  5. washThe resulting organic layer was washed with water (66.0 kg)
  6. dry with materiala 20% aqueous solution of sodium chloride (33.0 kg), and then dried over anhydrous sodium sulfate
  7. customThe solvent was then evaporated under reduced pressure
  8. customto give the target product as a yellow amorphous product (5.18 kg, quantitative)

Sources & evidence

ORD record
ord-43241b9850774b84ae57b32b7fc74c62
Source dataset
uspto-grants-2015_06
Patent number
US09045460B2

Reaction notes

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