Potassium Carbonate → 1-(3-phenylpyrrolidin-1-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473468Notes

Reaction equation

HRID 1473468 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:27]1([CH:33]2[CH2:37][CH2:36][NH:35][CH2:34]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C=O)C>[C:27]1([CH:33]2[CH2:37][CH2:36][N:35]([C:2]3[C:11]4[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]5[S:17][CH:18]=[CH:19][N:20]=5)(=[O:14])=[O:13])=[CH:9][CH:10]=4)[CH:5]=[CH:4][N:3]=3)[CH2:34]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 31467433-PhenylpyrrolidineHCID 866873831-chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Product 1

HCID 866875171-(3-phenylpyrrolidin-1-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

1-Chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (from Example 73, step 2; 0.050 g, 0.153 mmol) and potassium carbonate (0.106 g, 0.767 mmol) were dissolved in DMF (1.023 ml). 3-Phenyl-pyrrolidine (0.032 ml, 0.230 mmol) was added and the reaction was stirred overnight at 110° C. The reaction was filtered through a syringe filter and purified via HPLC (25 to 70% MeCN:H2O with 0.1% TFA modifier). The product fractions were combined and concentrated. The material was dissolved in methanol and passed through an SCX ion exchange column (pre-wetted with methanol). The column was flushed with methanol, then the product was liberated by flushing the column with 2 M ammonia in methanol. The filtrate was combined to afford 1-(3-phenylpyrrolidin-1-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.34 (d, J=8.9 Hz, 1H), 8.16 (d, J=1.9 Hz, 1H), 8.00 (d, J=5.6 Hz, 1H), 7.71 (dd, J=1.9, 8.9 Hz, 1H), 7.40-7.31 (m, 4H), 7.28-7.22 (m, 1H), 7.19 (d, J=5.6 Hz, 1H), 7.11 (d, J=4.2 Hz, 1H), 6.67 (d, J=4.3 Hz, 1H), 4.12-3.97 (m, 2H), 3.94-3.77 (m, 2H), 3.55-3.42 (m, 1H), 2.42-2.27 (m, 1H), 2.19-2.04 (m, 1H). m/z (ESI) 437.2 (M+H)+.

Workup

  1. filtrationThe reaction was filtered through a syringe
  2. filtrationfilter
  3. custompurified via HPLC (25 to 70% MeCN:H2O with 0.1% TFA modifier)
  4. concentrationconcentrated
  5. dissolutionThe material was dissolved in methanol
  6. customThe column was flushed with methanol
  7. customby flushing the column with 2 M ammonia in methanol

Sources & evidence

ORD record
ord-9583dd5d546248fc911c201ad60357eb
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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