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

HRID 895394

반응식

HRID 895394 반응식
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

참가 물질

9

반응물 5

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

생성물 1

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

시약·촉매·용매 3

HCID 73415796Chromium dioxide촉매HCID 6344Dichloromethane용매2회HCID 8857Ethyl Acetate용매

실험 절차

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. [Method modeled after M. J. Robins et al. J. Med. Chem., 35, 2283-2293 (1992)]

후처리

  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

출처 및 근거

ORD 기록
ord-c7247fbc740d4bd59919370ba6207987
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06916820B1

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