Hydrochloric Acid → HCID 66811622, compound

HRID 1099213Notes

Reaction equation

HRID 1099213 reaction equation
[CH2:1]([N:5]1[CH2:10][CH2:9][N:8]([CH:11]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:12]([NH:14][NH:15][C:16]([CH:18]2[CH:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:22][CH2:21][CH2:20][N:19]2C(OC(C)(C)C)=O)=O)=[O:13])[C:7](=[O:43])[C:6]1=[O:44])[CH2:2][CH2:3][CH3:4].CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC.Cl>ClCCCl.CCOC(C)=O>[CH2:1]([N:5]1[CH2:10][CH2:9][N:8]([CH:11]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:12]2[O:13][C:16]([C@H:18]3[C@@H:23]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:22][CH2:21][CH2:20][NH:19]3)=[N:15][N:14]=2)[C:7](=[O:43])[C:6]1=[O:44])[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamate2×HCID 66811749HCID 66811749, compound

Product 1

HCID 66811622HCID 66811622, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of tert-butyl 2-({2-[(4-butyl-2,3-dioxopiperazin-1-yl)(phenyl)acetyl]hydrazino}carbonyl)-3-phenylpiperidine-1-carboxylate (15.5 mg, 0.026 mmol) in 1,2-dichloroethane (1.5 ml) was added Burgess reagent (21.9 mg, 0.078 mmol). The reaction vessel was sealed and heated to 120° C. for 10 min in an Emry's Optimizer microwave reactor. Additional Burgess reagent (21.9 mg, 0.078 mmol) was added to the solution, and the reaction was sealed and heated again to 120° C. for 10 min in a microwave reactor. The reaction was concentrated in vacuo to yield the cyclodehydration product. A solution of the crude material in EtOAc (5 ml) at 0° C. was saturated with HCl gas and allowed to stir for 2 h. The reaction was concentrated in vacuo and purified via reverse phase HPLC to yield 1-butyl-4-(phenyl[5-(cis-3-phenylpiperidin-2-yl)-1,3,4-oxadiazol-2-yl]methyl)piperazine-2,3-dione. HRMS (ES, M+H), cal'd for C28H33N5O3: 488.2656, found: 488.2646. 1H NMR (400 MHz, CD3OD) δ 7.42-7.22 (m, 7H), 7.09 (m, 3H), 6.87 (m, 2H), 5.36 (dd, J=14.6, 5.4 Hz, 1H), 3.88 (t, J=13.2 Hz, 1H), 3.53 (m, 1H), 3.44 (m, 6H), 3.24 (m, 1H), 3.11 (m, 1H), 2.55-2.38 (m, 1H), 2.25 (m, 1H), 2.00 (m, 2H), 1.56 (m, 2H), 1.33 (sext, J=7.4 Hz, 2H), 0.94 (t, J=7.2 Hz, 3H).

Workup

  1. customThe reaction vessel was sealed
  2. customthe reaction was sealed
  3. temperatureheated again to 120° C. for 10 min in a microwave reactor
  4. concentrationThe reaction was concentrated in vacuo
  5. customto yield the cyclodehydration product
  6. customat 0° C.
  7. concentrationThe reaction was concentrated in vacuo
  8. custompurified via reverse phase HPLC

Sources & evidence

ORD record
ord-c8274cf95786471d8574ff9ec544c977
Source dataset
uspto-grants-2012_03
Patent number
US08143405B2

Reaction notes

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