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

HRID 450195ノート

反応式

HRID 450195 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-c0c11d6847b44244b8ddc74fde555027
出典データセット
uspto-grants-2013_07
特許番号
US08486939B2

反応ノート

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