Pyridine → tert-butyl(3S,4S)-5-acetyl-7-cyano-4-methyl-1-((2-methylnaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

HRID 1486113Notes

Reaction equation

HRID 1486113 reaction equation
[C:1]([C:3]1[CH:35]=[CH:34][C:6]2[N:7]([CH2:22][C:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH:26]=[CH:25][C:24]=3[CH3:33])[C:8](=[O:21])[C@@H:9]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[C@H:10]([CH3:12])[NH:11][C:5]=2[CH:4]=1)#[N:2].N1C=CC=CC=1.[C:42](Cl)(=[O:44])[CH3:43]>C(Cl)Cl>[C:42]([N:11]1[C@@H:10]([CH3:12])[C@H:9]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[C:8](=[O:21])[N:7]([CH2:22][C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=[CH:25][C:24]=2[CH3:33])[C:6]2[CH:34]=[CH:35][C:3]([C:1]#[N:2])=[CH:4][C:5]1=2)(=[O:44])[CH3:43]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 72714055tert-butyl(3S,4S)-7-cyano-4-methyl-1-((2-methylnaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

Product 1

HCID 72714056tert-butyl(3S,4S)-5-acetyl-7-cyano-4-methyl-1-((2-methylnaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamateYield 59.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of tert-butyl(3S,4S)-7-cyano-4-methyl-1-((2-methylnaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (364 mg, 774 μmol) in CH2Cl2 (7.74 ml) was added pyridine (306 mg, 315 μl, 3.87 mmol), followed by acetyl chloride (71.8 μl, 1.01 mmol), dropwise. The reaction was stirred at 0° C. for 1 h, then allowed to warm to rt and stirred for an additional 15 h, then quenched by the addition of H2O and extracted with CH2Cl2. The combined organic layers were washed with sat. aq. NaHCO3 and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl(3S,4S)-5-acetyl-7-cyano-4-methyl-1-((2-methylnaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (235 mg, 59%) as a white solid. MS m/z 535 (MNa)+.

Workup

  1. temperatureto warm to rt
  2. stirringstirred for an additional 15 h
  3. customquenched by the addition of H2O
  4. extractionextracted with CH2Cl2
  5. washThe combined organic layers were washed with sat. aq. NaHCO3 and sat. aq. NaCl
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-80224db0ccca46529ec0eae4041c1b62
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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