Triethylamine → 1-Chloro-isoquinoline-5-sulfonic acid {2-[2-(2-trifluoromethyl-phenoxy)-ethylamino]-ethyl}-amide

HRID 2219231Notes

Reaction equation

[F:1][C:2]([F:14])([F:13])[C:3]1[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=1[O:5][CH2:6][CH:7]=O.Cl.[NH2:16][CH2:17][CH2:18][NH:19][S:20]([C:23]1[C:24]2[CH:25]=[CH:26][N:27]=[C:28]([Cl:33])[C:29]=2[CH:30]=[CH:31][CH:32]=1)(=[O:22])=[O:21].CCN(CC)CC.[BH4-].[Na+]>CO>[F:1][C:2]([F:14])([F:13])[C:3]1[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=1[O:5][CH2:6][CH2:7][NH:16][CH2:17][CH2:18][NH:19][S:20]([C:23]1[C:24]2[CH:25]=[CH:26][N:27]=[C:28]([Cl:33])[C:29]=2[CH:30]=[CH:31][CH:32]=1)(=[O:21])=[O:22]

Participants

Conditions

Temperature: 0 °C

Procedure

A 4.2 mL of the (2-trifluoromethyl-phenoxy)-acetaldehyde stock solution (˜0.69 mmol) is added to a stirred mixture of 1-chloro-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amide hydrochloride (200 mg, 0.621 mmol), 4 Å molecular sieve (400 mg) and NEt3 (0.19 mL, 1.4 mmol) in anhydrous CH3OH (5 mL) at ambient temperature under nitrogen. The resultant mixture is stirred for 16 hours. The mixture is cooled to 0° C. before it is treated with powdered sodium borohydride (53 mg, 1.4 mmol). The mixture is stirred at 0° C. for 1 hour and at ambient temperature for another 1 hour. After filtration and subsequent concentration in vacuo, the crude product is chromatographed on silica (gradient 0-5% CH3OH in CH2Cl2) to give 92 mg (0.19 mmol, 31% yield) of 1-chloro-isoquinoline -5-sulfonic acid {2-[2-(2-trifluoromethyl-phenoxy)-ethylamino]-ethyl}-amide. ESIMS: m/z 474 [(M+H)+, 35Cl], 476 [(M+H)+, 37Cl].

Workup

filtrationAfter filtration and subsequent concentration in vacuo
customthe crude product is chromatographed on silica (gradient 0-5% CH3OH in CH2Cl2)

Sources & evidence

ORD record: ord-3ae807e264a142d9a2104a02dfc166cf
Source dataset: uspto-grants-2008_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07414063B2

Reaction notes

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