Potassium Phosphate, Tribasic → 7-(3-Difluoromethylphenyl)-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amide

HRID 269986Notes

Reaction equation

C(OC(=O)[NH:7][CH2:8][CH2:9][NH:10][S:11]([C:14]1[C:15]2[CH:16]=[CH:17][N:18]=[CH:19][C:20]=2[CH:21]=[C:22](Br)[CH:23]=1)(=[O:13])=[O:12])(C)(C)C.[F:26][CH:27]([F:37])[C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.CO.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:7][CH2:8][CH2:9][NH:10][S:11]([C:14]1[C:15]2[CH:16]=[CH:17][N:18]=[CH:19][C:20]=2[CH:21]=[C:22]([C:32]2[CH:31]=[CH:30][CH:29]=[C:28]([CH:27]([F:37])[F:26])[CH:33]=2)[CH:23]=1)(=[O:12])=[O:13]

Participants

Conditions

Temperature: 82 °C

Procedure

Dissolve [2-(7-bromo-isoquinoline-5-sulfonylamino)-ethyl]-carbamic acid tert-butyl ester (0.13 g, 0.30 mmol) and 3-(difluoromethyl)phenylboronic acid (0.057 g, 0.33 mmol) in DME-methanol (8:1, 10 ml). To the mixture, add K3PO4 (0.13 g, 0.60 mmol), and PdCl2(dppf) (0.012 g, 0.015 mmol). Heat this mixture at 82° C. overnight. Cool the reaction mixture, dilute with water and extract with EtOAc. Wash with brine and evaporate to dryness. Purify by silica gel chromatography to give the desired compound (0.10 g, 71% yield): 1H NMR (CDCl3): δ9.39 (s, 1H), 8.66 (m, 2H), 8.43 (d, J=5.7 Hz, 2H), 7.86 (m, 2H), 7.61 (m, 2H), 6.76 (t, J=52.1 Hz, 1H), 5.00 (br s, 1H), 3.18 (m, 2H), 3.03 (m, 2H), 1.37 (s, 9H); ESIMS: m/z 478 (M+H)+.

Workup

temperatureCool the reaction mixture
extractionextract with EtOAc
washWash with brine
customevaporate to dryness
customPurify by silica gel chromatography

Sources & evidence

ORD record: ord-1c02f53ad4f34396a0e03e34fad62472
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07449477B2

Reaction notes

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