Sodium bis(trimethylsilyl)amide → HCID 56949508, compound

HRID 1626365Notes

Reaction equation

HRID 1626365 reaction equation
[Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([NH:9][CH2:10][C:11]2[S:15][C:14]([CH3:16])=[N:13][C:12]=2[CH3:17])[N:5]=[C:4]([O:18][CH2:19][CH2:20][OH:21])[N:3]=1.Br[C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[N:24]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([O:18][CH2:19][CH2:20][O:21][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[N:26][CH:27]=[CH:28][CH:29]=3)[N:24]=2)[N:5]=[C:6]([NH:9][CH2:10][C:11]2[S:15][C:14]([CH3:16])=[N:13][C:12]=2[CH3:17])[C:7]=1[CH3:8]

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 47382232-bromo-1,8-naphthyridineHCID 86688163HCID 86688163, compound

Product 1

HCID 56949508HCID 56949508, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2-[(4-chloro-6-{[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]amino}-5-methylpyrimidin-2-yl)oxy]ethanol G1 (17 mg, 0.052 mmol) and 2-bromo-1,8-naphthyridine (11 mg, 0.053 mmol) were placed in a test tube and dissolved in THF (1 mL). A 2 M solution of NaHMDS in THF (39 μL, 0.078 mmol) was added at ambient temperature, and the reaction was stirred overnight. Solvent was then removed, and the product was purified by silica gel flash column chromatography (EtOAc/hexanes gradient). 10 mg (42%) of G2 were isolated as an off-white solid. 1H NMR (499 MHz, DMSO-d6): δ 8.97 (s, 1H); 8.56 (d, J=8.03 Hz, 1H); 8.44 (d, J=8.81 Hz, 1H); 7.89-7.84 (m, 1H); 7.62 (dd, J=7.95, 4.62 Hz, 1H); 7.26 (d, J=8.79 Hz, 1H); 4.78 (d, J=5.18 Hz, 2H); 4.66 (d, J=4.97 Hz, 2H); 4.57 (d, J=5.78 Hz, 2H); 2.47 (s, 3H); 2.30 (s, 3H); 2.01 (s, 3H). HRMS (Electrospray): m/z 457.1206 (MH+).

Workup

  1. customSolvent was then removed
  2. customthe product was purified by silica gel flash column chromatography (EtOAc/hexanes gradient)
  3. custom10 mg (42%) of G2 were isolated as an off-white solid

Sources & evidence

ORD record
ord-2f8de6b09ce044ddac36c807981ba839
Source dataset
uspto-grants-2014_07
Patent number
US08785467B2

Reaction notes

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