6-Methylpyrimidin-4-amine → HCID 86687647, compound

HRID 1473585Notes

Reaction equation

HRID 1473585 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:24]4[C:19](=[CH:20][C:21]([S:25](OC5C(F)=C(F)C(F)=C(F)C=5F)(=[O:27])=[O:26])=[CH:22][CH:23]=4)[CH:18]=[CH:17][N:16]=3)=[C:11]([O:40][CH3:41])[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:42][C:43]1[N:48]=[CH:47][N:46]=[C:45]([NH2:49])[CH:44]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:24]4[C:19](=[CH:20][C:21]([S:25]([NH:49][C:45]5[CH:44]=[C:43]([CH3:42])[N:48]=[CH:47][N:46]=5)(=[O:26])=[O:27])=[CH:22][CH:23]=4)[CH:18]=[CH:17][N:16]=3)=[C:11]([O:40][CH3:41])[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

5

Reactant 3

HCID 5728526-Methylpyrimidin-4-amineHCID 2733832Lithium HexamethyldisilazideHCID 86687644HCID 86687644, compound

Product 1

HCID 86687647HCID 86687647, compoundYield 47.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A vial was charged with perfluorophenyl 1-(3′,5′-difluoro-3-methoxy-[1,1′-biphenyl]-4-yl)isoquinoline-6-sulfonate (INTERMEDIATE KKKKK; 63.5 mg, 0.107 mmol), 6-methylpyrimidin-4-amine (12.26 mg, 0.112 mmol), and THF (535 μl). The vial was cooled in an ice-water bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (225 μl, 0.225 mmol) was added. After 20 min of stirring, the mixture was loaded directly onto a silica gel loading column. The column was eluted onto a pre-equilibrated 12-g Redi-Sep Gold column with 0-10% MeOH/DCM to give an orange solid. This solid was resubjected to chromatography on silica gel (12-g Redi-Sep Gold column, 4.5% MeOH/DCM) to give 1-(3′,5′-difluoro-3-methoxy-[1,1′-biphenyl]-4-yl)-N-(6-methylpyrimidin-4-yl)isoquinoline-6-sulfonamide (26.22 mg, 0.051 mmol, 47.3% yield) as a light-pink solid. 1H NMR (400 MHz, DMSO-d6) δ=13.48-12.42 (m, 1H), 8.75-8.62 (m, 2H), 8.47 (s, 1H), 8.11 (d, J=5.6 Hz, 1H), 7.95 (d, J=9.1 Hz, 1H), 7.75 (d, J=8.7 Hz, 1H), 7.63 (d, J=6.9 Hz, 2H), 7.57-7.48 (m, 2H), 7.46-7.40 (m, 1H), 7.34-7.23 (m, 1H), 7.06-6.86 (m, J=17.2 Hz, 1H), 3.77 (s, 3H), 2.31 (s, 3H). m/z (ESI) 519.0 (M+H)+.

Workup

  1. temperatureThe vial was cooled in an ice-water bath for 10 min
  2. washThe column was eluted onto a pre-equilibrated 12-g Redi-Sep Gold column with 0-10% MeOH/DCM
  3. customto give an orange solid

Sources & evidence

ORD record
ord-c06b73d63db741e78f7e45ffed292c79
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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