Acetic Acid → (Rac)-2-chloro-9-cyclopentyl-7-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

HRID 2111272Notes

Reaction equation

HRID 2111272 reaction equation
C(O)C.C(O)(=O)C.C[O:9][C:10](=O)[CH:11]([CH3:27])[CH2:12][N:13]([C:19]1[C:24]([NH2:25])=[CH:23][N:22]=[C:21]([Cl:26])[N:20]=1)[CH:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1>CCOCC>[Cl:26][C:21]1[N:22]=[CH:23][C:24]2[NH:25][C:10](=[O:9])[CH:11]([CH3:27])[CH2:12][N:13]([CH:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[C:19]=2[N:20]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 702EthanolHCID 87619052(Rac)-3-[(5-amino-2-chloro-pyrimidin-4-yl)-cyclopentyl-amino]-2-methyl-propanoic acid methyl ester

Product 1

HCID 87617699(Rac)-2-chloro-9-cyclopentyl-7-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-oneYield 65.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A mixture of 1500 mL of ethanol, 25 mL of acetic acid and 35.2 g of the (rac)-3-[(5-amino-2-chloro-pyrimidin-4-yl)-cyclopentyl-amino]-2-methyl-propanoic acid methyl ester (V-1) prepared in the previous step was heated at reflux overnight, and then concentrated under reduced pressure. The residue was taken up in dichloromethane and washed successively with 10% sodium bicarbonate solution, and then water and dried over anhydrous sodium sulfate. The mixture was filtered and then concentrated under reduced pressure to give 31 g of the crude product. Trituration of the residue with ether, provided 20.7 g of (rac)-2-chloro-9-cyclopentyl-7-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-1).

Workup

  1. customprepared in the previous step
  2. temperaturewas heated
  3. temperatureat reflux overnight
  4. concentrationconcentrated under reduced pressure
  5. washwashed successively with 10% sodium bicarbonate solution
  6. dry with materialwater and dried over anhydrous sodium sulfate
  7. filtrationThe mixture was filtered
  8. concentrationconcentrated under reduced pressure
  9. customto give 31 g of the crude product

Sources & evidence

ORD record
ord-28dcb2c35daf4e6eb72e33b6ab70ff77
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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