Ammonium Chloride → 2-Chloro-9-cyclopentyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 2279990Notes

Reaction equation

HRID 2279990 reaction equation
[CH:1]1([N:6]([C:13]2[C:18]([N+:19]([O-])=O)=[CH:17][N:16]=[C:15]([Cl:22])[N:14]=2)[CH2:7][CH2:8][C:9](OC)=[O:10])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH4+].[Cl-]>[Fe].CCO.O>[Cl:22][C:15]1[N:16]=[CH:17][C:18]2[NH:19][C:9](=[O:10])[CH2:8][CH2:7][N:6]([CH:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[C:13]=2[N:14]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 57940528Methyl 3-[cyclopentyl(2-chloro-5-nitropyrimidin-4-yl)amino]propanoate

Product 1

HCID 579403592-Chloro-9-cyclopentyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 43.7%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 19096565Water ethanolSolvent

Procedure

Methyl 3-[cyclopentyl(2-chloro-5-nitropyrimidin-4-yl)amino]propanoate (1.00 g, 0.003 mol) and NH4Cl (1.38 g, 0.025 mol, 8.5 eq) were added to EtOH/H2O (4:1 ml, 10 ml) and the mixture heated to reflux before the portion-wise addition of iron powder (1.36 g, 0.024 mol, 8 eq). The RM was then refluxed for an additional 2 h. Progress of the reaction was monitored by HPLC and when no SM remained the RM was filtered hot through celite. The celite was washed with EtOAc (10 ml) and EtOH (10 ml) [both hot] and the filtrate evaporated under reduced pressure and further dried in vacuo to give the product as a brown solid (350 mg, 43%); Rt=12 min (Vydac 1); MS+ve: 267.2.

Workup

  1. temperaturethe mixture heated
  2. temperatureThe RM was then refluxed for an additional 2 h
  3. filtrationwas filtered hot through celite
  4. washThe celite was washed with EtOAc (10 ml) and EtOH (10 ml) [both hot] and the filtrate
  5. customevaporated under reduced pressure
  6. customfurther dried in vacuo

Sources & evidence

ORD record
ord-a19cbeacbbb641f3b946e40595d11875
Source dataset
uspto-grants-2015_09
Patent number
US09133199B2

Reaction notes

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