4-Aminopyrimidine → HCID 86687629, compound

HRID 1473567Notes

Reaction equation

HRID 1473567 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([O:21]C4C(F)=C(F)C(F)=C(F)C=4F)(=O)=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)=[C:4]([CH3:33])[CH:3]=1.[N:34]1[CH:39]=[CH:38][C:37]([NH2:40])=[N:36][CH:35]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:16](=[CH:15][C:14]([S:18]([NH:40][C:37]4[CH:38]=[CH:39][N:34]=[CH:35][N:36]=4)(=[O:19])=[O:21])=[CH:13][CH:12]=3)[CH:11]=[CH:10][N:9]=2)=[C:4]([CH3:33])[CH:3]=1

Participants

5

Reactant 3

HCID 689584-AminopyrimidineHCID 2733832Lithium HexamethyldisilazideHCID 86687627HCID 86687627, compound

Product 1

HCID 86687629HCID 86687629, compoundYield 45.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A round-bottom flask was charged with perfluorophenyl 1-(4-chloro-2-methylphenyl)isoquinoline-6-sulfonate (INTERMEDIATE DDDDD, 189 mg, 0.378 mmol), pyrimidin-4-amine (39.6 mg, 0.416 mmol), and THF (1891 μl) to give a clear, lightly-colored solution. The flask was cooled in an ice-bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (794 μl, 0.794 mmol) was added drop wise over 30 s to give a yellow suspension. After 15 min, the mixture was quenched by the addition of TFA (0.3 mL), and then concentrated. The residue was concentrated from DCM then from MeOH. The residue was then purified by chromatography on silica gel (12-g Redi-Sep Gold column, 5-10% MeOH/DCM). Fractions containing product were combined and concentrated. The residue was taken up in DCM and filtered. The collected solid was washed with DCM (3×), then dried under a stream of N2 (g) for 20 min to give 1-(4-chloro-2-methylphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (70.2 mg, 0.171 mmol, 45.2% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.72 (d, J=5.7 Hz, 2H), 8.58 (br. s., 1H), 8.26 (br. s., 1H), 8.16 (d, J=5.4 Hz, 1H), 8.00-7.94 (m, 1H), 7.69 (d, J=8.3 Hz, 1H), 7.53 (d, J=2.0 Hz, 1H), 7.46-7.40 (m, 1H), 7.36-7.30 (m, 1H), 7.05 (s, 1H), 1.98 (s, 3H). m/z (ESI) 411.2 (M+H)+.

Workup

  1. customto give a clear, lightly-colored solution
  2. temperatureThe flask was cooled in an ice-bath for 5 min
  3. customto give a yellow suspension
  4. customthe mixture was quenched by the addition of TFA (0.3 mL)
  5. concentrationconcentrated
  6. concentrationThe residue was concentrated from DCM
  7. customThe residue was then purified by chromatography on silica gel (12-g Redi-Sep Gold column, 5-10% MeOH/DCM)
  8. additionFractions containing product
  9. concentrationconcentrated
  10. filtrationfiltered
  11. washThe collected solid was washed with DCM (3×)
  12. dry with materialdried under a stream of N2 (g) for 20 min

Sources & evidence

ORD record
ord-9f1e096bb1f842efa5827f209a306755
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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