2-Methylpyrimidin-4-amine → HCID 86687646, compound

HRID 1473584Notes

Reaction equation

HRID 1473584 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]=[C:47]([NH2:49])[CH:46]=[CH:45][N: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:47]5[CH:46]=[CH:45][N:44]=[C:43]([CH3:42])[N:48]=5)(=[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

Participants

5

Reactant 3

HCID 2957632-Methylpyrimidin-4-amineHCID 2733832Lithium HexamethyldisilazideHCID 86687644HCID 86687644, compound

Product 1

HCID 86687646HCID 86687646, compoundYield 50.5%

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; 64.75 mg, 0.109 mmol), 2-methylpyrimidin-4-amine (12.50 mg, 0.115 mmol), and THF (546 μl) (not all the amine dissolved). The vial was cooled in an ice-water bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (229 μl, 0.229 mmol) was added. After 40 min, 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 0-5% MeOH/DCM to give 1-(3′,5′-difluoro-3-methoxy-[1,1′-biphenyl]-4-yl)-N-(2-methylpyrimidin-4-yl)isoquinoline-6-sulfonamide (28.4 mg, 0.055 mmol, 50.2% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=13.32 (br. s., 1H), 8.68 (d, J=5.7 Hz, 1H), 8.62 (s, 1H), 8.17-8.03 (m, 2H), 7.95 (dd, J=1.7, 8.9 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.68-7.59 (m, 2H), 7.56-7.48 (m, 2H), 7.46-7.39 (m, 1H), 7.29 (tt, J=2.2, 9.3 Hz, 1H), 6.90 (br. s., 1H), 3.77 (s, 3H), 2.35 (s, 3H). m/z (ESI) 519.0 (M+H)+.

Workup

  1. dissolutiondissolved)
  2. temperatureThe vial was cooled in an ice-water bath for 10 min
  3. washThe column was eluted onto a pre-equilibrated 12-g Redi-Sep Gold column with 0-5% MeOH/DCM

Sources & evidence

ORD record
ord-9f75a8014a20463c988d385e8465a4fb
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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