2-Aminothiazole → 1-(4-cyano-2-methoxyphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473442Notes

Reaction equation

HRID 1473442 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[CH:12]=[CH:11][N:10]=2)=[C:5]([O:34][CH3:35])[CH:4]=1)#[N:2].[S:36]1[CH:40]=[CH:39][N:38]=[C:37]1[NH2:41].C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C(Cl)Cl>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19]([NH:41][C:37]4[S:36][CH:40]=[CH:39][N:38]=4)(=[O:20])=[O:21])=[CH:16][CH:17]=3)[CH:12]=[CH:11][N:10]=2)=[C:5]([O:34][CH3:35])[CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 86687486Perfluorophenyl 1-(4-cyano-2-methoxyphenyl)isoquinoline-6-sulfonate

Product 1

HCID 866874871-(4-cyano-2-methoxyphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamideYield 101%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A vial was charged with perfluorophenyl 1-(4-cyano-2-methoxyphenyl)isoquinoline-6-sulfonate (67.07 mg, 0.132 mmol), thiazol-2-amine (13.26 mg, 0.132 mmol), and THF (662 μl) to give a clear, colorless solution. The vial was cooled in an ice-water bath for 15 min, then lithium bis(trimethylsilyl)amide (1M in THF) (265 μl, 0.265 mmol) was added drop wise. After 20 min, the mixture was loaded onto a 5-g silica gel loading column with DCM. The column was dried under vacuum for 5 min then eluted onto a pre-equilibrated 12-g column with 0 to 10% MeOH/DCM to give 1-(4-cyano-2-methoxyphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (56.25 mg, 0.133 mmol, 101% yield) as an off-white foam: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.89 (br. s., 1H), 8.70 (d, J=5.7 Hz, 1H), 8.56 (d, J=1.8 Hz, 1H), 8.14 (d, J=5.3 Hz, 1H), 7.87 (dd, J=1.9, 8.8 Hz, 1H), 7.74 (d, J=1.3 Hz, 1H), 7.68 (d, J=8.8 Hz, 1H), 7.64-7.59 (m, 1H), 7.56-7.52 (m, 1H), 7.28 (d, J=4.6 Hz, 1H), 6.88 (d, J=4.6 Hz, 1H), 3.72 (s, 3H); m/z (ESI) 423.2 (M+H)+.

Workup

  1. customto give a clear, colorless solution
  2. temperatureThe vial was cooled in an ice-water bath for 15 min
  3. customThe column was dried under vacuum for 5 min
  4. washthen eluted onto a pre-equilibrated 12-g column with 0 to 10% MeOH/DCM

Sources & evidence

ORD record
ord-5abf93903315410ab9aaf5a7df9389aa
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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