Hydrochloric Acid → HCID 86714322, compound

HRID 333011Notes

Reaction equation

C(S([O:6][C:7]1[CH:12]=[C:11]([C:13]([CH3:39])([CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@H:20]([CH2:24][O:25][C:26]3[C:35]4[C:34]([NH2:36])=[N:33][S:32](=[O:38])(=[O:37])[NH:31][C:30]=4[CH:29]=[CH:28][CH:27]=3)[CH2:19]2)=[O:17])[CH3:14])[CH:10]=[CH:9][C:8]=1[O:40][CH3:41])(=O)=O)C.[OH-].[Na+].Cl>CCO>[NH2:36][C:34]1[C:35]2[C:26]([O:25][CH2:24][C@H:20]3[CH2:21][CH2:22][CH2:23][N:18]([C:16](=[O:17])[CH2:15][C:13]([C:11]4[CH:10]=[CH:9][C:8]([O:40][CH3:41])=[C:7]([OH:6])[CH:12]=4)([CH3:39])[CH3:14])[CH2:19]3)=[CH:27][CH:28]=[CH:29][C:30]=2[NH:31][S:32](=[O:38])(=[O:37])[N:33]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of (S)-5-(4-(3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidin-1-yl)-2-methyl-4-oxobutan-2-yl)-2-methoxyphenyl methanesulfonate (200 mg, 0.34 mmol) (Example 50) in EtOH (20 mL) was added 2N aqueous NaOH (0.34 mL). The reaction mixture was stirred at 85° C. for 3 hours, cooled to 0° C. and neutralized 2N HCl. The solution was concentrated under reduced pressure and purified by preparative HPLC (10-90% acetonitrile in water) to give the title compound (78 mg, 45%). 1H NMR (400 MHz, DMSO-d6) δ 1.17-1.32 (m, 8H), 1.43-1.64 (m, 2H), 1.74-1.8 (m, 1H), 2.52-2.67 (m, 2H), 2.77-2.83 (m, 0.5H), 3.51-3.54 (m, 0.5H), 3.65-3.68 (m, 4H), 3.73-3.84 (m, 2H), 4.1-4.18 (m, 1H), 5.9-5.94 (m, 1H), 6.15-6.19 (m, 1H), 6.5 (brs, 1H), 6.66-6.78 (m, 3H), 6.89-6.95 (m, 1H), 8.71 (s, 1H). MS 517 (MH+).

Workup

temperaturecooled to 0° C.
concentrationThe solution was concentrated under reduced pressure
custompurified by preparative HPLC (10-90% acetonitrile in water)

Sources & evidence

ORD record: ord-9c292c07ece5446c8307b772d6e719d9
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08877922B2

Reaction notes

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