Hydrochloric Acid → HCID 66811616, compound

HRID 1099215Notes

Reaction equation

HRID 1099215 reaction equation
[CH3:1][N:2]([CH2:40][C@@H:41]1[CH2:43][C@H:42]1[CH3:44])[C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([N:34]([CH3:39])[S:35]([CH3:38])(=[O:37])=[O:36])[N:33]=1)[C:6]([NH:8][NH:9][C:10]([C@H:12]1[C@@H:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:16][CH2:15][CH2:14][N:13]1C(OC(C)(C)C)=O)=O)=[O:7].CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC.Cl>ClCCCl.CCOC(C)=O>[CH3:39][N:34]([C:32]1[CH:31]=[C:5]([C:6]2[O:7][C:10]([C@H:12]3[C@@H:17]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH2:16][CH2:15][CH2:14][NH:13]3)=[N:9][N:8]=2)[CH:4]=[C:3]([N:2]([CH3:1])[CH2:40][C@@H:41]2[CH2:43][C@H:42]2[CH3:44])[N:33]=1)[S:35]([CH3:38])(=[O:36])=[O:37]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 66811685HCID 66811685, compound

Product 1

HCID 66811616HCID 66811616, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of tert-butyl cis-2-[(2-{2-(methyl[(trans-2-methylcyclopropyl)methyl]amino)-6-[methyl(methylsulfonyl)amino]isonicotinoyl}hydrazino)carbonyl]-3-phenylpiperidine-1-carboxylate (93.7 mg, 0.15 mmol) in 1,2-dichloroethane (1.5 ml) was added Burgess reagent (162 mg, 0.60 mmol). The reaction vessel was sealed and heated to 120° C. for 10 min in an Emry's Optimizer microwave reactor. The reaction was concentrated in vacuo and purified via reverse phase HPLC to yield the cyclodehydration product. A solution of the material in EtOAc (15 ml) at 0° C. was saturated with HCl gas and allowed to stir for 1 h. The reaction was concentrated in vacuo and purified via reverse phase HPLC to yield title example N-methyl-N-(6-(methyl[(trans-2-methylcyclopropyl)methyl]amino)-4-[5-(cis-3-phenylpiperidin-2-yl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl)methanesulfonamide. HRMS (ES, M+H), cal'd for C26H34N6O3S: 511.2486. found: 511.2475. 1H NMR (400 MHz, CD3OD) δ 7.32 (m, 3H), 7.19 (d, J=7.3 Hz, 2H), 6.78 (m, 1H), 6.55 (m, 1H), 5.45 (d, J=5.1 Hz, 1H), 3.99 (m, 1H), 3.62 (m, 1H), 3.54 (m, 2H), 3.38 (m, 1H), 3.34 (s, 3H), 3.14 (s, 3H), 3.10 (s, 3H), 2.43-2.27 (m, 2H), 2.03 (m, 2H), 1.04 (d, J=5.7 Hz, 3H), 0.73 (m, 2H), 0.46 (m, 1H), 0.26 (m, 1H).

Workup

  1. customThe reaction vessel was sealed
  2. concentrationThe reaction was concentrated in vacuo
  3. custompurified via reverse phase HPLC
  4. customto yield the cyclodehydration product
  5. customat 0° C.
  6. concentrationThe reaction was concentrated in vacuo
  7. custompurified via reverse phase HPLC

Sources & evidence

ORD record
ord-0707a5638a724361952c77b59ef864de
Source dataset
uspto-grants-2012_03
Patent number
US08143405B2

Reaction notes

Loading…