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

HRID 450195Notes

Reaction equation

HRID 450195 reaction equation
[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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-c0c11d6847b44244b8ddc74fde555027
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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