Hydrochloric Acid → (Rac)-7-(6-amino-5,6,7,8-tetrahydronaphthalen-2-yl)-9-cyclopropyl-6-fluoro-9h-isothiazolo[5,4-b]quinoline-3,4-dione

HRID 1640961Notes

Reaction equation

HRID 1640961 reaction equation
Cl.C(Cl)Cl.C(OC(=O)[NH:11][CH:12]1[CH2:21][CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:22]3[CH:31]=[C:30]4[C:25]([C:26](=[O:39])[C:27]5[C:37](=[O:38])[NH:36][S:35][C:28]=5[N:29]4[CH:32]4[CH2:34][CH2:33]4)=[CH:24][C:23]=3[F:40])[CH:18]=2)[CH2:13]1)(C)(C)C>C(O)(=O)C>[NH2:11][CH:12]1[CH2:21][CH2:20][C:19]2[CH:18]=[C:17]([C:22]3[CH:31]=[C:30]4[C:25]([C:26](=[O:39])[C:27]5[C:37](=[O:38])[NH:36][S:35][C:28]=5[N:29]4[CH:32]4[CH2:34][CH2:33]4)=[CH:24][C:23]=3[F:40])[CH:16]=[CH:15][C:14]=2[CH2:13]1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 6344Dichloromethane2×HCID 58426875(Rac)-tert-butyl[6-(9-cyclopropyl-6-fluoro-3,4-dioxo-2,3,4,9-tetrahydro-isothiazolo[5,4-b]quinolin-7-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

Product 1

HCID 59999527(Rac)-7-(6-amino-5,6,7,8-tetrahydronaphthalen-2-yl)-9-cyclopropyl-6-fluoro-9h-isothiazolo[5,4-b]quinoline-3,4-dione

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

In air, a solution of hydrogen chloride in acetic acid (1 M, 1.8 mL) is added at room temperature to a solution of methylene chloride (0.6 mL) containing (rac)-tert-Butyl[6-(9-cyclopropyl-6-fluoro-3,4-dioxo-2,3,4,9-tetrahydro-isothiazolo[5,4-b]quinolin-7-yl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (11.4 mg, 0.022 mmol). A yellow precipitate begins to appear within minutes of addition of the solution of hydrogen chloride. After stirring the mixture at room temperature for 18 h, additional methylene chloride is added (2 mL). The precipitate is collected by filtration, washed with methylene chloride (4×5 mL), and dried in vacuo to give pure 31 (97% purity by HPLC analysis) as a yellow powder. mp >257-258° C. dec. 1H NMR (DMSO-d6, 60° C.): δ 1.21 (m, 2H, c-Pr CH2), 1.29 (m, 2H, c-Pr CH2), 1.80 (m, 1H, H-3), 2.12 (m, 1H, H-3), 2.83 (dd, J=17.0 Hz, 10.0 Hz, 1H, H-1), 2.90 (m, 2H, H-4), 3.13 (dd, J=17.0 Hz, 6.0 Hz, 1H, H-1), 3.46 (m, 1H, H-2), 3.57 (m, 1H, c-Pr CH), 7.25 (d, J=8.0 Hz, 1H, H-8), 7.37 (s, 1H, H-5), 7.39 (d, J=8.0 Hz, 1H, H-7), 7.93 (d, JH-F=10.5 Hz, 1H, ITQ H-5), 8.01 (d, JH-F=6.5 Hz, 1H, ITQ H-8). 19F{1H} NMR (DMSO-d6, 60° C.): δ −123.3 (s). NMR spectra collected at room temperature contained broad, unresolved signals. LCMS m/z calcd for C23H20FN3O2S ([M]+) 421. Found 422 ([M+H]+). HRMS m/z calcd for C23H20FN3NaO2S ([M+Na]+) 444.1158. Found 444.1152.

Workup

  1. filtrationThe precipitate is collected by filtration
  2. washwashed with methylene chloride (4×5 mL)
  3. customdried in vacuo
  4. customto give pure 31 (97% purity by HPLC analysis) as a yellow powder
  5. customNMR spectra collected at room temperature

Sources & evidence

ORD record
ord-0722276113914cd9bad76bd56753c507
Source dataset
uspto-grants-2012_02
Patent number
US08114888B2

Reaction notes

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