3-Aminopyridine → 2-chloro-6-(4-morpholinyl)-5-nitro-N-(3-pyridinyl)-4-pyrimidinamine

HRID 450193Notes

Reaction equation

HRID 450193 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:5]([N+:14]([O-:16])=[O:15])=[C:4](Cl)[N:3]=1.[NH2:18][C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([NH:18][C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)[C:5]([N+:14]([O-:16])=[O:15])=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:7]=1

Participants

5

Reactant 3

HCID 100093-AminopyridineHCID 2733832Lithium HexamethyldisilazideHCID 215178494-Morpholino-5-nitro-2,6-dichloropyrimidine

Product 1

HCID 866497812-chloro-6-(4-morpholinyl)-5-nitro-N-(3-pyridinyl)-4-pyrimidinamineYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture 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) (1.89 g, 3.6 mmol) and 3-aminopyridine (0.68 g, 7.2 mmol) in THF at −70° C. was treated with 7.2 mL of LiHMDS (1M solution in THF, 2 eq.) and the mixture was stirred at that temperature for 1.5 hrs, and then allowed to warm to room temperature. The solvent was removed and the crude product was extracted with 0.5 M HCl. After filtration, the aqueous solution was made basic with sat. Na2CO3, to give a precipitate, which was collected by filtration, and dried, to give 1.12 g (52% yield) of 2-chloro-6-(4-morpholinyl)-5-nitro-N-(3-pyridinyl)-4-pyrimidinamine: mp (aq. MeOH)>310° C.; 1H NMR (CDCl3) δ 10.19 (br s, 1H), 8.74 (d, J=2.5 Hz, 1H), 8.45 (dd, J=4.8, 1.4 Hz, 1H), 8.12 (ddd, J=8.3, 2.6, 1.5 Hz, 1H), 7.35 (dd, J=8.4, 4.8 Hz, 1H), 3.81 (m, 4H), 3.61 (m, 4H).

Workup

  1. customat −70° C.
  2. customThe solvent was removed
  3. extractionthe crude product was extracted with 0.5 M HCl
  4. filtrationAfter filtration
  5. customto give a precipitate, which
  6. filtrationwas collected by filtration
  7. customdried

Sources & evidence

ORD record
ord-c745ac9f53c049f8b61badd575d529f3
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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