Hydrochloric Acid → HCID 46836669, compound

HRID 383437Notes

Reaction equation

HRID 383437 reaction equation
C(OC([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)[C:17]([O:25]C(OC)=O)=[CH:16][C:15]=2[NH:30][C:31]([CH:33]2[O:38][C:37]3[CH:39]=[CH:40][C:41]([C:43]#[N:44])=[CH:42][C:36]=3[N:35](C(OCC)=O)[CH2:34]2)=[O:32])[CH2:10][CH2:9]1)=O)(C)(C)C.[OH-].[Na+].Cl>CO.O>[C:43]([C:41]1[CH:40]=[CH:39][C:37]2[O:38][CH:33]([C:31]([NH:30][C:15]3[CH:16]=[C:17]([OH:25])[C:18]([CH:20]4[CH2:21][CH2:22][CH2:23][CH2:24]4)=[CH:19][C:14]=3[C:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH:10]=3)=[O:32])[CH2:34][NH:35][C:36]=2[CH:42]=1)#[N:44]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67459094HCID 67459094, compound

Product 1

HCID 46836669HCID 46836669, compoundYield 19.7%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
60 °C

Procedure

Ethyl 2-(2-(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-4-cyclopentyl-5-(methoxycarbonyloxy)phenylcarbamoyl)-6-cyano-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate (50 mg, 0.08 mmol) and NaOH (162 mg, 4.05 mmol) were dissolved in 5:1 methanol/water (3.6 mL) and heated at 60° C. for 2 h. The mixture was added to 1N HCl (25 mL) and extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. Removal of the Boc protecting group was achieved by dissolving the compound in dichloromethane (3.0 mL) and TFA (3.0 mL) and stirring for 10 min before being concentrated in vacuo. HPLC purification (10-99% CH3CN/0.05% TFA) provided 6-cyano-N-(4-cyclopentyl-5-hydroxy-2-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamide (7 mg, 19% yield). LC/MS m/z 562.2 [M+H]+. 1H NMR (400.0 MHz, MeOD) δ 9.56 (s, 1H), 9.15 (s, 1H), 7.16 (s, 1H), 7.01 (m, 3H), 6.90 (s, 1H), 6.45 (s, 1H), 5.56 (s, 1H), 4.89 (q, J=3.0 Hz, 1H), 3.61 (s, 2H), 3.56-3.53 (m, 1H), 3.44-3.39 (m, 1H), 3.33 (m, obscured by H2O peak, 1H), 3.23-3.16 (m, 3H), 2.44 (s, 2H), 1.93 (m, 1.97-1.90, 2H), 1.78-1.71 (m, 2H), 1.65-1.62 (m, 2H), 1.56-1.45 (m, 2H).

Workup

  1. extractionextracted with ethyl acetate (3×10 mL)
  2. dry with materialThe combined organic extracts were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customRemoval of the Boc protecting group
  6. dissolutionby dissolving the compound in dichloromethane (3.0 mL)
  7. concentrationbefore being concentrated in vacuo
  8. customHPLC purification (10-99% CH3CN/0.05% TFA)

Sources & evidence

ORD record
ord-a9643b0c075e424b8f4ff11ef063ae83
Source dataset
uspto-grants-2013_02
Patent number
US08367660B2

Reaction notes

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