Water → HCID 90112233, compound

HRID 1509045Notes

Reaction equation

HRID 1509045 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([B:20]4[O:24]C(C)(C)C(C)(C)[O:21]4)=[CH:16][CH:15]=3)[C:10]([CH2:29][CH3:30])=[C:9]([CH3:31])[N:8]=2)=[CH:4][CH:3]=1.F.[F-].[K+].O>CO>[Cl:1][C:2]1[S:6][C:5]([C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([B:20]([OH:24])[OH:21])=[CH:16][CH:15]=3)[C:10]([CH2:29][CH3:30])=[C:9]([CH3:31])[N:8]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 11829350Potassium bifluorideHCID 90111505HCID 90111505, compound

Product 1

HCID 90112233HCID 90112233, compoundYield 23.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 18-mL vial was charged with 2-(5-chloro-2-thienyl)-5-ethyl-6-methyl-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-4-amine (10.3 mg, 0.023 mmol) and potassium hydrogen difluoride (40 mg, 0.5 mmol). Water (0.2 ml) and MeOH (1 ml) were added respectively. The resulting mixture was stirred at rt for 1 hr. Then the volatile material was removed under reduced pressure. The residue was treated with trimethylsilyl chloride (0.1 ml) in a mixture of acetonitrile (1 ml) and water (0.2 ml). After the mixture was stirred at rt for 1 hr, the volatile material was removed the residue was treated with NaHCO3 aq. (5 ml). The precipitate was collected and purified by Preparative TLC plate using 5% of acetone in DCM as mobile phase to give the title compound (2 mg, 23% yield). MW=373.66. 1H NMR (Methanol-d4, 400 MHz) δ 7.87 (d, J=8.4 Hz, 2H), 7.74 (d, J=8.4 Hz, 2H), 7.67 (d, J=4.0 Hz, 1H), 6.93 (d, J=4.0 Hz, 1H), 2.67 (q, J=7.6 Hz, 2H), 2.54 (s, 3H), 1.21 (t, J=7.6 Hz, 3H).

Workup

  1. customThen the volatile material was removed under reduced pressure
  2. additionThe residue was treated with trimethylsilyl chloride (0.1 ml) in a mixture of acetonitrile (1 ml) and water (0.2 ml)
  3. stirringAfter the mixture was stirred at rt for 1 hr
  4. customthe volatile material was removed the residue
  5. additionwas treated with NaHCO3 aq. (5 ml)
  6. customThe precipitate was collected
  7. custompurified by Preparative TLC plate

Sources & evidence

ORD record
ord-486fc4ab65954f6ba91290ea12d42fb0
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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