Dimethylformamide → HCID 86687518, compound

HRID 1473469Notes

Reaction equation

HRID 1473469 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=3[O:30][CH3:31])[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.[CH3:32][N:33]([CH:35]=O)[CH3:34].[CH3:37][N:38]1C=CC=C1[Sn](CCCC)(CCCC)CCCC>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:31][O:30][C:23]1[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:22]=1[CH2:21][N:15]([C:16]1[S:17][CH:18]=[CH:19][N:20]=1)[S:12]([C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[C:2]([C:32]1[N:33]([CH3:34])[CH:35]=[CH:37][N:38]=1)=[N:3][CH:4]=[CH:5]2)(=[O:13])=[O:14]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 27693971-methyl-2-(tributylstannyl)-1H-pyrroleHCID 866873781-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Product 1

HCID 86687518HCID 86687518, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A microwave vial was charged with 1-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate OOO; 0.050 g, 0.105 mmol), Pd(Ph3P)4 (0.012 g, 10.50 μmol), and DMF (0.525 ml). 1-Methyl-2-(tributylstannyl)-1H-pyrrole (0.078 ml, 0.210 mmol) was added and the reaction was heated in a microwave reactor at 90° C. for 30 minutes. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via silica gel column chromatography (12 g, gradient elution 0 to 100% EtOAc:Heptane with a 10% MeOH/DCM flush) to afford N-(2,4-dimethoxybenzyl)-1-(1-methyl-1H-imidazol-2-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as an off-white solid. m/z (ESI) 522.2 (M+H)+. The material was dissolved in DCM and TFA (8.09 μl, 0.105 mmol) was added. The reaction was stirred for 30 minutes at room temperature. The reaction was concentrated, triturated with diethyl ether, and filtered. The solids were washed with diethyl ether and the filtrate was concentrated and purified via column chromatography (12 g silica gel column, gradient elution 0 to 10% MeOH:EtOAc) to afford 1-(1-methyl-1H-pyrrol-2-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=12.93 (br. s., 1H), 9.12 (s, 1H), 8.81 (d, J=5.7 Hz, 1H), 8.64 (s, 1H), 8.34 (d, J=9.0 Hz, 1H), 8.26 (d, J=5.6 Hz, 1H), 8.10 (s, 1H), 8.00 (dd, J=1.9, 8.9 Hz, 1H), 7.30 (d, J=4.5 Hz, 1H), 6.89 (d, J=4.5 Hz, 1H), 3.88 (s, 3H). m/z (ESI) 371.1 (M+H)+.

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialthe combined organic layers were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe material was purified via silica gel column chromatography (
  7. wash12 g, gradient elution 0 to 100% EtOAc
  8. customHeptane with a 10% MeOH/DCM flush)

Sources & evidence

ORD record
ord-b45e8d5b50d645d28585372b84c81fbd
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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