2-Benzimidazolepropanol → 2-[3-(1H-benzimidazol-2-yl)propoxy]-6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methylpyrimidin-4-amine

HRID 1626364Notes

Reaction equation

HRID 1626364 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](S(C)(=O)=O)[N:5]=[C:4]([NH:12][CH2:13][C:14]2[S:18][C:17]([CH3:19])=[N:16][C:15]=2[CH3:20])[C:3]=1[CH3:21].[NH:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[N:24]=[C:23]1[CH2:31][CH2:32][CH2:33][OH:34].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[NH:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[N:24]=[C:23]1[CH2:31][CH2:32][CH2:33][O:34][C:6]1[N:5]=[C:4]([NH:12][CH2:13][C:14]2[S:18][C:17]([CH3:19])=[N:16][C:15]=2[CH3:20])[C:3]([CH3:21])=[C:2]([Cl:1])[N:7]=1

Participants

5

Reactant 3

HCID 754702-BenzimidazolepropanolHCID 2724254Sodium bis(trimethylsilyl)amideHCID 866881616-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methyl-2-methylsulfonyl-pyrimidin-4-amine

Product 1

HCID 569494492-[3-(1H-benzimidazol-2-yl)propoxy]-6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methylpyrimidin-4-amineYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methyl-2-methylsulfonyl-pyrimidin-4-amine F5 (480 mg, 1.384 mmol) and 3-(1H-benzimidazol-2-yl)propan-1-ol (244 mg, 1.38 mmol) were placed in a 20 mL vial and dissolved in THF (5 mL). A 1 M solution of NaHMDS in THF (1.38 mL, 1.38 mmol) was added, and the reaction was stirred overnight. Solvent was then removed, and the product was purified by silica gel flash column chromatography (EtOAc/hexanes gradient). 500 mg (82%) of F6 were isolated as an off-white foam. 1H NMR δ (300 MHz, DMSO-d6): 7.84-7.80 (1H, m), 7.76 (2H, dd, J=6.20, 3.18 Hz), 7.51 (2H, dd, J=6.28, 3.15 Hz), 4.46 (2H, d, J=5.76 Hz), 4.37-4.31 (2H, m), 2.54 (4H, s), 2.46 (3H, s), 2.29 (3H, s), 1.99 (3H, s). HRMS (Electrospray): m/z 443.1413 (MH+).

Workup

  1. customSolvent was then removed
  2. customthe product was purified by silica gel flash column chromatography (EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-6c502a3edabd4e73a4fcff19328b72c2
Source dataset
uspto-grants-2014_07
Patent number
US08785467B2

Reaction notes

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