Hydrochloric Acid → 2-Amino-5-(4-chlorophenoxy)-4-(4-oxocyclohexylamino)pyrimidine hydrochloride

HRID 1370286

Reaction equation

HRID 1370286 reaction equation
C(OC(=O)C)(=O)C.N1C=CC=CC=1.NC1N=C(N[C@H]2CC[C@H](O)CC2)C(OC2C=CC([Cl:36])=CC=2)=CN=1.[NH2:37][C:38]1[N:43]=[C:42]([NH:44][CH:45]2[CH2:50][CH2:49][C:48](=[O:51])[CH2:47][CH2:46]2)[C:41]([O:52][C:53]2[CH:58]=[CH:57][C:56]([Cl:59])=[CH:55][CH:54]=2)=[CH:40][N:39]=1.Cl>ClCCl.[O-2].[Cr+4].[O-2].C(OCC)(=O)C>[ClH:36].[NH2:37][C:38]1[N:43]=[C:42]([NH:44][CH:45]2[CH2:50][CH2:49][C:48](=[O:51])[CH2:47][CH2:46]2)[C:41]([O:52][C:53]2[CH:54]=[CH:55][C:56]([Cl:59])=[CH:57][CH:58]=2)=[CH:40][N:39]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 7918Acetic AnhydrideHCID 98190002-Amino-5-(4-chlorophenoxy)-4-(4-oxocyclohexylamino)pyrimidineHCID 178508527HCID 178508527, compound

Product 1

HCID 223805432-Amino-5-(4-chlorophenoxy)-4-(4-oxocyclohexylamino)pyrimidine hydrochlorideYield 41%

Reagents, catalysts & solvents 3

HCID 73415796Chromium dioxideCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Acetic anhydride (0.61 g, 5.8 mmoles) and pyridine (0.96 g, 11.9 mmoles) were added to an ice-bath cooled suspension of chromium(IV) oxide (Aldrich) (0.61 g, 6.1 mmoles) in dichloromethane (11 mL). The mixture was stirred at ambient temperature for 20 minutes, and 2-amino-5-(4-chlorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine (0.65 g, 1.87 mmoles) was added, followed by dichloromethane (10 mL). The mixture was stirred for 1.25 hours and poured into cold ethyl acetate (200 mL), stirred for 15 minutes and filtered through a pad of Celite 545 (Fisher). The filtrate was filtered through flutted filter paper and then spin evaporated in vacuo. The residue was purified by flash column chromatography on Silica Gel 60 (E.M. Science, 230-440 mesh) (2×16 cm) using ethyl acetate as the eluant. The fractions that contained homogeneous product were spin evaporated in vacuo to give a syrup. The flash column chromatography was repeated. The pure 2-amino-5-(4-chlorophenoxy)-4-(4-oxocyclohexylamino)pyrimidine was converted to the hydrochloride by the same procedure described in Example 4. The residue was triturated under ethyl acetate to give a white solid which was collected, washed with ethyl acetate and dried in vacuo to give 0.29 g (41% yield) of 2-amino-5-(4-chlorophenoxy)-4-(4-oxocyclohexylamino)pyrimidine hydrochloride as a white solid.

Workup

  1. temperaturecooled
  2. stirringThe mixture was stirred for 1.25 hours
  3. stirringstirred for 15 minutes
  4. filtrationfiltered through a pad of Celite 545 (Fisher)
  5. filtrationThe filtrate was filtered
  6. filtrationthrough flutted filter paper
  7. customspin evaporated in vacuo
  8. customThe residue was purified by flash column chromatography on Silica Gel 60 (E.M. Science, 230-440 mesh) (2×16 cm)
  9. customwere spin evaporated in vacuo
  10. customto give a syrup
  11. customThe residue was triturated under ethyl acetate
  12. customto give a white solid which
  13. customwas collected
  14. washwashed with ethyl acetate
  15. customdried in vacuo

Sources & evidence

ORD record
ord-aa2cb9431d32442da98c72b5e7a4861c
Source dataset
uspto-grants-2003_06
Patent number
US06583148B1

Linked notes

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