Hydrochloric Acid → HCID 67003445, compound

HRID 1970806Notes

Reaction equation

[C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:14]([NH2:17])=[N:15][CH:16]=2)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].C(N([CH2:30][CH3:31])CC)C.[I:32][C:33]1[CH:43]=[CH:42][C:36]([CH2:37][S:38](Cl)(=[O:40])=[O:39])=[CH:35][CH:34]=1.Cl>ClCCl>[C:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]2[N:12]=[C:13]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:14]([N:17]([S:38]([CH2:37][C:31]3[CH:30]=[CH:43][C:33]([I:32])=[CH:34][CH:35]=3)(=[O:40])=[O:39])[S:38]([CH2:37][C:36]3[CH:42]=[CH:43][C:33]([I:32])=[CH:34][CH:35]=3)(=[O:40])=[O:39])=[N:15][CH:16]=2)=[CH:9][CH:10]=1)(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

Under an argon atmosphere, 5-(4-acetoxyphenyl)-2-amino-3-benzylpyrazine (c-19) (681 mg, 2.13 mmol) was dissolved in anhydrous dichloromethane (40 mL), and to this was added triethylamine (1.20 mL, 8.53 mmol), and cooled to 0° C. To this was added 4-iodobenzylsulfonyl chloride (prepared by the method described in Liu, S. et al., Org. Lett., 3, 1571-1574 (2001)) (2.70 g, 8.53 mmol), and heated to reflux for 26 h after warming to room temperature. After cooling to room temperature, to this were added 2 M hydrochloric acid and dichloromethane and after separating the aqueous layer and organic layer, the organic layer was washed once with water and once with saturated brine, and dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated under reduced pressure with a rotary evaporator. The residue was purified by silica gel column chromatography (100 g, n-hexane/ethyl acetate=4/1), to the obtained product was added dichloromethane, and filtered to remove insolubles. After this procedure was repeated 5 times, the filtrate was concentrated under reduced pressure with a rotary evaporator. The residue was recrystallized from ethyl acetate to give 5-(4-acetoxyphenyl)-3-benzyl-2-bis(4-iodobenzylsulfonyl)aminopyrazine (c-46) as a colorless solid (597 mg, 31.8%). Rf=0.21 (n-hexane/ethyl acetate=4/1). Mp. 166-167° C. 1H NMR. (400 MHz, DMSO-d6) δ 2.30 (s, 3H), 3.89 (s, 2H), 5.00 (d, 2H, J=13.6 Hz), 5.19 (d, 2H, J=13.6 Hz), 7.11-7.17 (AA′BB′, 2H), 7.19-7.34 (m, 9H), 7.78-7.83 (AA′BB′, 4H), 8.07-8.15 (AA′BB′, 2H), 9.19 (s, 1H). 13C NMR (67.8 MHz, DMSO-d6) δ 20.9, 37.5, 60.5 (2C), 96.3, 126.4, 126.5 (2C), 128.1 (2C), 128.5 (2C), 129.5 (2C), 132.0, 133.6 (4C), 137.4, 137.7 (4C), 139.2, 140.9, 151.2, 152.5, 155.5, 168.9. IR (KBr, cm−1) 519, 575, 627, 704, 775, 835, 912, 1013, 1057, 1159, 1200, 1254, 1356, 1377, 1483, 1601, 1757. Anal. Calcd. For C33H27I2N3O6S2: C, 45.06; H, 3.09; N, 4.78. Found: C, 45.18; H, 3.24; N, 4.78.

Workup

customprepared by the method
temperature, 3, 1571-1574 (2001)) (2.70 g, 8.53 mmol), and heated
temperatureto reflux for 26 h
temperatureafter warming to room temperature
temperatureAfter cooling to room temperature
customafter separating the aqueous layer and organic layer
washthe organic layer was washed once with water and once with saturated brine
dry with materialdried over anhydrous sodium sulfate
customAfter removing anhydrous sodium sulfate
filtrationby filtration
concentrationthe filtrate was concentrated under reduced pressure with a rotary evaporator
customThe residue was purified by silica gel column chromatography (100 g, n-hexane/ethyl acetate=4/1), to the obtained product
additionwas added dichloromethane
filtrationfiltered
customto remove insolubles
concentrationthe filtrate was concentrated under reduced pressure with a rotary evaporator
customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record: ord-27f0b4b2e6da4b3d858378ed553861be
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431525B2

Reaction notes

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