Ethanol → 2'-chloro-9'-cyclopentyl-8',9'-dihydrospiro[cyclopropane-1,7'-pyrimido[4,5-b][1,4]diazepin]-6'(5'H)-one

HRID 2111383Notes

Reaction equation

HRID 2111383 reaction equation
C[O:2][C:3]([C:5]1([CH2:8][N:9]([C:15]2[C:20]([NH2:21])=[CH:19][N:18]=[C:17]([Cl:22])[N:16]=2)[CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH2:7][CH2:6]1)=O.C(O)C>C(O)(=O)C>[Cl:22][C:17]1[N:18]=[CH:19][C:20]2[NH:21][C:3](=[O:2])[C:5]3([CH2:7][CH2:6]3)[CH2:8][N:9]([CH:10]3[CH2:14][CH2:13][CH2:12][CH2:11]3)[C:15]=2[N:16]=1

Participants

4

Reactant 2

HCID 702EthanolHCID 866234201-{[(5-Amino-2-chloro-pyrimidin-4-yl)-cyclopentyl-amino]-methyl}-cyclopropanecarboxylic acid methyl ester

Product 1

HCID 579698732'-chloro-9'-cyclopentyl-8',9'-dihydrospiro[cyclopropane-1,7'-pyrimido[4,5-b][1,4]diazepin]-6'(5'H)-oneYield 98%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 0.2224 g (0.00068 mole) of 1-{[(5-amino-2-chloro-pyrimidin-4-yl)-cyclopentyl-amino]-methyl}-cyclopropanecarboxylic acid methyl ester (V-53), 12 mL of ethanol and 0.3 mL of acetic acid was heated at reflux for 18 hours, and then concentrated under reduced pressure. The residue was dissolved in 100 mL of ethyl acetate and washed successively twice with 15 mL of aqueous sodium bicarbonate, twice with 15 mL of brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 0.195 g of 2-chloro-9-cyclopentyl-8,9-dihydro-spiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1′-cyclopropan]-6(7H)-one (VI-53), as a light yellow solid.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 18 hours
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in 100 mL of ethyl acetate
  5. washwashed successively twice with 15 mL of aqueous sodium bicarbonate, twice with 15 mL of brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-92492c2aa3fc42748cbb0f2e750d8fe2
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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