Acetonitrile--water (1/1) → HCID 86664031, compound

HRID 712318Notes

Reaction equation

HRID 712318 reaction equation
C([O:3][C:4]([C:6]1([CH2:37][CH3:38])[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20](/[CH:33]=[N:34]/OC)[C:21]4[S:25][C:24]([NH:26][C:27](=[O:31])[NH:28][CH2:29][CH3:30])=[N:23][C:22]=4[CH:32]=3)=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])C.[OH2:39].CC#N>CO.[OH-].[Na+].O>[C:33]([C:20]1[C:21]2[S:25][C:24]([NH:26][C:27](=[O:31])[NH:28][CH2:29][CH3:30])=[N:23][C:22]=2[CH:32]=[C:18]([C:15]2[CH:14]=[N:13][C:12]([N:9]3[CH2:8][CH2:7][C:6]([CH2:37][CH3:38])([C:4]([OH:3])=[O:5])[CH2:11][CH2:10]3)=[N:17][CH:16]=2)[CH:19]=1)(=[O:39])[NH2:34]

Participants

6

Reactant 2

HCID 18373917Acetonitrile--water (1/1)HCID 87222522HCID 87222522, compound

Product 1

HCID 86664031HCID 86664031, compoundYield 5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
65 °C

Procedure

Ethyl-4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-[(E)-methoxyiminomethyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylate (619 mg, 1.147 mmol) 100 was suspended in MeOH (9 mL) and NaOH(aq) (1M, 9 mL), sealed in a microwave vessel, irradiated at 85° C. for 1 h, followed by conventionally heating overnight at 65° C. The reaction was diluted with water (40 mL) and washed with EtOAc (1×50 mL). Acidification of the aqueous phase with HCl(aq) (1M, pH 2) and back extracting with EtOAc (3×60 mL) yielded a waxy solid which was subjected directly to reverse phase chromatography (5-100% H2O/MeCN) yielding 25 mg (5% yield) of the Compound 193 as a by-product to the aldoxime. 1H NMR (DMSO-d6) δ 8.84 (s, 2H), 8.33 (s, 1H), 8.11 (d, J=1.4 Hz, 1H), 8.03 (d, J=1.4 Hz, 1H), 7.71 (s, 1H), 6.87 (t, J=5.4 Hz, 1H), 4.46 (dd, J=9.9, 3.6 Hz, 2H), 3.18 (qd, J=13.2, 4.8 Hz, 4H), 2.06 (d, J=13.4 Hz, 2H), 1.54 (q, J=7.4 Hz, 2H), 1.35 (td, J=13.6, 4.0 Hz, 2H), 1.11 (t, J=7.2 Hz, 3H), 0.81 (t, J=7.5 Hz, 3H). MS: 498.2 [M+H]+.

Workup

  1. customirradiated at 85° C. for 1 h
  2. washwashed with EtOAc (1×50 mL)
  3. extractionAcidification of the aqueous phase with HCl(aq) (1M, pH 2) and back extracting with EtOAc (3×60 mL)
  4. customyielded a waxy solid which

Sources & evidence

ORD record
ord-262b06a4c2384ff3a9b0bb99779c5b45
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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