Diisopropylethylamine → 3,5-Diamino-N-(N-{4-[6-(tert-butyldimethylsilyloxy)naphthalen-2-yl]butyl}carbamimidoyl)-6-chloropyrazine-2-carboxamide

HRID 2036262Notes

Reaction equation

[Si:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([CH2:19][CH2:20][CH2:21][CH2:22][NH2:23])[CH:13]=[CH:12]2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH2:24][C:25]1[C:26]([C:33]([NH:35][C:36](SC)=[NH:37])=[O:34])=[N:27][C:28]([Cl:32])=[C:29]([NH2:31])[N:30]=1.C(N(C(C)C)CC)(C)C>CCO>[NH2:24][C:25]1[C:26]([C:33]([NH:35][C:36](=[NH:37])[NH:23][CH2:22][CH2:21][CH2:20][CH2:19][C:14]2[CH:13]=[CH:12][C:11]3[C:16](=[CH:17][CH:18]=[C:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH:10]=3)[CH:15]=2)=[O:34])=[N:27][C:28]([Cl:32])=[C:29]([NH2:31])[N:30]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of amine 77 (337 mg, 1.02 mmole) and methyl 3,5-diamino-6-chloropyrazine-2-carbonylcarbamimidothioate (10, 596 mg, 1.53 mmole) in EtOH (20 mL) was added diisopropylethylamine (1.06 mL, 6.13 mmole) at room temperature. The reaction mixture was heated at 70° C. in a sealed tube for 6 h, then cooled to room temperature, and concentrated to dryness. The residue was purified by column chromatography (silica gel, 80:18:2 CHCl3/CH3OH/NH4OH) to afford carboxamide 78 (280 mg, 50%) as a light yellow solid: 1H NMR (300 MHz, CD3OD) δ 7.67 (d, J=9.2 Hz, 1H), 7.63 (d, J=8.6 Hz, 1H), 7.57 (br s, 1H), 7.30 (d, J=8.1 Hz, 1H), 7.14 (br s, 1H), 7.03 (dd, J=9.2, 1.7 Hz, 1H), 3.30 (m, 2H), 2.81 (t, J=7.0 Hz, 2H), 1.95-1.62 (m, 4H), 1.03 (s, 9H), 0.24 (s, 6H).

Workup

temperaturecooled to room temperature
concentrationconcentrated to dryness
customThe residue was purified by column chromatography (silica gel, 80:18:2 CHCl3/CH3OH/NH4OH)

Sources & evidence

ORD record: ord-b202bc1e179e47e2a9a28654d493460b
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08575176B2

Reaction notes

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