(S)-2-(2-Methoxyethyl)piperazine → (S)-7-Chloro-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene

HRID 131459Notes

Reaction equation

[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[NH:6][C:7]3[S:8][C:9]([CH3:16])=[CH:10][C:11]=3[C:12](SC)=[N:13][C:4]=2[CH:3]=1.[CH3:19][O:20][CH2:21][CH2:22][C@H:23]1[CH2:28][NH:27][CH2:26][CH2:25][NH:24]1>C(O)(C)C>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[NH:6][C:7]3[S:8][C:9]([CH3:16])=[CH:10][C:11]=3[C:12]([N:27]3[CH2:26][CH2:25][NH:24][C@@H:23]([CH2:22][CH2:21][O:20][CH3:19])[CH2:28]3)=[N:13][C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 79.5 °C

Procedure

Combine 7-chloro-2-methyl-10-methylsulfanyl-4H-3-thia-4,9-diaza-benzo[f]azulene (42.74 g, 145 mmol) and (s)-2-(2-methoxy-ethyl)-piperazine (26.1 g, 181 mmol) in isopropyl alcohol (190 mL). Heat to 78-81° C. for 3-4 days, and then allow cooling to ambient temperature. Filter the solids and rinse with 1:1 MTBE/Ligroin (2×300 mL). Drying at 30° C. affords 39.1 g (69.5%) of the title compound: 1H NMR (500 MHz, DMSO-d6): δ 1.52 (bm, 2H), 2.27 (s, 3H), 2.45 (bt, 1H), 2.65 (bm, 2H), 2.75 (bt, 1H), 2.86 (bd, 1H), 3.20 (s, 3H), 3.38 (m, 2H), 3.80 (m, 1H), 3.90 (m, 1H), 6.33 (s, 1H), 6.67 (d, 1H), 6.75 (d, 1H), 6.82 (dd, 1H), 7.70 (s, 1H). 13C NMR (100 MHz, DMSO-d6): δ 15.07, 25.49, 33.28, 45.11, 47.36, 52.55, 57.92, 69.18, 118.38, 119.81, 122.29, 122.56, 126.41, 126.99, 128.43, 142.54, 142.90, 152.84, 157.82. MS (ES+) M+H calcd for C19H23ClN4OS 390.94; found 391.96.

Workup

temperatureallow cooling to ambient temperature
filtrationFilter the solids
washrinse with 1:1 MTBE/Ligroin (2×300 mL)
customDrying at 30° C.

Sources & evidence

ORD record: ord-6f734c0612bf42f6a630e80a23234393
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07384934B2

Reaction notes

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