Acetic Acid → 2-chloro-6-(4-morpholinyl)-5-nitro-N-(5-pyrimidinyl)-4-pyrimidinamine

HRID 450195노트

반응식

HRID 450195 반응식
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl:18][C:19]1[N:24]=[C:23]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[C:22]([N+:31]([O-:33])=[O:32])=[C:21](Cl)[N:20]=1.C(O)(=O)C>C1COCC1.O>[Cl:18][C:19]1[N:20]=[C:21]([NH:1][C:2]2[CH:3]=[N:4][CH:5]=[N:6][CH:7]=2)[C:22]([N+:31]([O-:33])=[O:32])=[C:23]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[N:24]=1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 344373Pyrimidin-5-amineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 215178494-Morpholino-5-nitro-2,6-dichloropyrimidine

생성물 1

HCID 866497822-chloro-6-(4-morpholinyl)-5-nitro-N-(5-pyrimidinyl)-4-pyrimidinamine수율 65%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

To 0.482 g (5.06 mmol) of 5-aminopyrimidine in THF (10 mL) was added 2.90 mL of NaHMDS (2 M solution in THF) at 0° C., and the mixture was stirred for 10 min. A solution of 0.5924 g (2.12 mmol) of 4-(2,6-dichloro-5-nitro-4-pyrimidinyl)morpholine (U.S. Pat. Appl. Publ. No. 2009/0181963, the disclosure of which is incorporated herein by reference in its entirety) in THF (5 mL) was added, and the resulting mixture was stirred for 15 min. The reaction mixture was neutralized with acetic acid, diluted with water, and extracted with EtOAc. The organic layer was washed with water and aq. NH3, dried, and concentrated. Chromatography on silica, eluting with hexanes/EtOAc (8:2), gave 0.465 g (65% yield) of 2-chloro-6-(4-morpholinyl)-5-nitro-N-(5-pyrimidinyl)-4-pyrimidinamine as a white powder: 1H NMR (DMSO-d6) δ 10.34 (s, 1H), 8.98 (s, 1H), 8.92 (s, 2H), 3.70 (t, J=4.8 Hz, 4H), 3.50 (t, J=4.8 Hz, 4H).

후처리

  1. additionwas added
  2. stirringthe resulting mixture was stirred for 15 min
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with water and aq. NH3
  5. customdried
  6. concentrationconcentrated
  7. washChromatography on silica, eluting with hexanes/EtOAc (8:2)

출처 및 근거

ORD 기록
ord-c0c11d6847b44244b8ddc74fde555027
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486939B2

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