Lithium Hexamethyldisilazide → HCID 9907029, compound

HRID 1166063Notes

Reaction equation

HRID 1166063 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[C:5]2=[N:12][N:13]=[C:14]([C:15]3[CH:19]=[C:18]([CH3:20])[O:17][N:16]=3)[N:4]2[N:3]=1.[CH3:21][N:22]1[C:26]([CH2:27][OH:28])=[N:25][CH:24]=[N:23]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CN(C)C=O>[CH3:20][C:18]1[O:17][N:16]=[C:15]([C:14]2[N:4]3[N:3]=[C:2]([O:28][CH2:27][C:26]4[N:22]([CH3:21])[N:23]=[CH:24][N:25]=4)[C:11]4[C:6]([C:5]3=[N:12][N:13]=2)=[CH:7][CH:8]=[CH:9][N:10]=4)[CH:19]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 11073377(1-methyl-1H-1,2,4-triazol-5-yl)methanolHCID 15453930HCID 15453930, compound

Product 1

HCID 9907029HCID 9907029, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 5-chloro-3-(5-methylisoxazol-3-yl)-1,2,3a,4,6-pentaaza-cyclopenta[a]naphthalene (100 mg, 0.35 mmol) in N,N-dimethyl formamide (7 ml) was added to a solution of 2-methyl-1,2,4-triazole-3-methanol (43 mg, 0.38 mmol) (prepared using the conditions of Itoh and Okongi, EP-A-421210) under nitrogen, and the mixture cooled to −78° C. Lithium bis(trimethylsilyl)amide (0.42 ml, 1.0 M in tetrahydrofuran, 0.42 mmol) was added, and the reaction stirred at −78° C. for 2 h, then allowed to warm to room temperature and stirred for 3 h. The solvents were evaporated by azeotroping with xylene and the residue pre-absorbed onto silica (1 g) from methanol/dichloromethane. Flash chromatography on a silica bond elute cartridge (10 g) eluting with a 0%→5% methanol/dichloromethane gradient, followed by recrystallisation (dichloromethane/ethyl acetate) gave the title-product (52 mg, 41%), mp 255-257° C.; 1H NMR (360 MHz, CDCl3) δ 9.16 (1H, dd, J=4.4 Hz and 1.7 Hz, Ar—H), 9.01 (1H, dd, J=8.2 Hz and 1.7 Hz, Ar—H), 7.92 (1H, m, Ar—H), 7.90 (1H, s, Ar—H), 6.93 (1H, s, Ar—H), 5.88 (2H, s, CH2), 4.12 (3H, s, CH3), 2.60 (3H, s, CH3); MS (ES+) m/e 364 [MH]+.

Workup

  1. customprepared
  2. temperatureto warm to room temperature
  3. stirringstirred for 3 h
  4. customThe solvents were evaporated
  5. customby azeotroping with xylene
  6. customthe residue pre-absorbed onto silica (1 g) from methanol/dichloromethane
  7. washFlash chromatography on a silica bond elute cartridge (10 g)
  8. washeluting with a 0%→5% methanol/dichloromethane gradient
  9. customfollowed by recrystallisation (dichloromethane/ethyl acetate)

Sources & evidence

ORD record
ord-ca6a1e2f81c04107afe511cd4122089a
Source dataset
uspto-grants-2003_09
Patent number
US06613766B1

Reaction notes

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