Potassium Phosphate, Tribasic → 3-(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide

HRID 1524402Notes

Reaction equation

HRID 1524402 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][C:7]([S:11]([N:14]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:22]=3[O:29][CH3:30])[C:15]3[S:19][N:18]=[CH:17][N:16]=3)(=[O:13])=[O:12])=[CH:8][CH:9]=2)[NH:4][CH:3]=1.[Cl:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[C:34]([C:41]2[N:45]([CH3:46])[N:44]=[CH:43][CH:42]=2)[CH:33]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([C:2]2[C:10]3[C:5](=[CH:6][C:7]([S:11]([N:14]([CH2:20][C:21]4[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:22]=4[O:29][CH3:30])[C:15]4[S:19][N:18]=[CH:17][N:16]=4)(=[O:13])=[O:12])=[CH:8][CH:9]=3)[NH:4][CH:3]=2)=[C:34]([C:41]2[N:45]([CH3:46])[N:44]=[CH:43][CH:42]=2)[CH:33]=1

Participants

4

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 71258743(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)boronic acid2×HCID 712592863-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide

Product 1

HCID 712592093-(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamideYield 72.6%

Conditions

Temperature
90 °C

Procedure

A microwave vial was charged with 3-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (83.6 mg, 0.164 mmol), (4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)boronic acid (Intermediate F) (50.4 mg, 0.213 mmol), potassium phosphate (105 mg, 0.492 mmol), and Pd(AmPhos)2Cl2 (5.81 mg, 8.21 μmol). The vial was flushed with Ar, then dioxane (0.6 mL) and water (0.2 mL) were added. The vial was sealed and heated in a microwave reactor for 20 min at 90° C. The mixture was extracted with EtOAc (3×), and the combined organic extracts were concentrated. The crude product was purified by chromatography on silica gel (0 to 100% EtOAc/Heptane) to give 3-(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (74 mg, 0.119 mmol, 72.6% yield) as an off-white foam. 1H NMR (400 MHz, DMSO-d6) δ=11.81 (s, 1 H), 8.34 (s, 1 H), 8.01-7.94 (m, 1 H), 7.70-7.58 (m, 3 H), 7.55-7.51 (m, 1 H), 7.45 (dd, J=1.9, 8.6 Hz, 1 H), 7.36 (d, J=1.9 Hz, 1 H), 7.16 (s, 1 H), 6.91 (d, J=8.4 Hz, 1 H), 6.45 (d, J=2.4 Hz, 1 H), 6.37 (dd, J=2.4, 8.5 Hz, 1 H), 6.28 (d, J=1.9 Hz, 1 H), 5.08 (s, 2 H), 3.72 (s, 3 H), 3.68 (s, 3 H), 3.21 (s, 3 H). m/z (ESI) 621.0 (M+H)+.

Workup

  1. customThe vial was flushed with Ar
  2. additiondioxane (0.6 mL) and water (0.2 mL) were added
  3. customThe vial was sealed
  4. extractionThe mixture was extracted with EtOAc (3×)
  5. concentrationthe combined organic extracts were concentrated
  6. customThe crude product was purified by chromatography on silica gel (0 to 100% EtOAc/Heptane)

Sources & evidence

ORD record
ord-d39a250fa6f64adab8ef278cd790013c
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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