1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 117599013, compound

HRID 522394Notes

Reaction equation

HRID 522394 reaction equation
[C:1]([C@H:5]1[C:40](=[O:41])[N:39]2[CH2:42][C@@H:36]([CH2:37][C@H:38]2[C:43]([NH:45][C@:46]2([C:51](O)=[O:52])[CH2:48][C@H:47]2[CH:49]=[CH2:50])=[O:44])[O:35][C:17]2=[N:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:24]=3[C:25]([O:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[C:16]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]2[CH2:54][CH2:55][CH2:56][C@H:9]2[O:8][C:7](=[O:57])[NH:6]1)([CH3:4])([CH3:3])[CH3:2].[CH3:58][N:59]([CH3:64])[S:60](=[O:63])(=[O:62])[NH2:61].CCN(C(C)C)C(C)C.C1CCN2C(=NCCC2)CC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CN(C1C=CN=CC=1)C.CCOCC.C(OCC)(=O)C>[C:1]([C@H:5]1[C:40](=[O:41])[N:39]2[CH2:42][C@@H:36]([CH2:37][C@H:38]2[C:43]([NH:45][C@:46]2([C:51](=[O:52])[NH:61][S:60](=[O:63])(=[O:62])[N:59]([CH3:64])[CH3:58])[CH2:48][C@H:47]2[CH:49]=[CH2:50])=[O:44])[O:35][C:17]2=[N:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:24]=3[C:25]([O:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)=[C:16]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]2[CH2:54][CH2:55][CH2:56][C@H:9]2[O:8][C:7](=[O:57])[NH:6]1)([CH3:2])([CH3:3])[CH3:4]

Participants

10

Reactant 5

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 81531DiisopropylethylamineHCID 134472N,N-DimethylsulfamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117598986HCID 117598986, compound

Product 1

HCID 117599013HCID 117599013, compoundYield 64.7%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the acid from Step 2 (46.6 mg) and N,N-dimethylsulfuric diamide (29.3 mg) in DMF (1 mL) was added DIPEA (52 DMAP (28.8 mg) and DBU (40 μL). The reaction mixture was stirred 5 minutes before adding HATU (26.9 mg). The mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with Et2O and ethyl acetate and quenched with water and acetic acid (pH=4). The mixture was extracted with diethyl ether (3×). The combined organic phases were washed with water (3×), dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography (ISCO, 0 to 10% methanol in dichloromethane) afforded the desired product (34.2 mg). LRMS (ES+) m/z 896.50 (M+H)+. By following the procedures outlined in Example 106 and using the appropriate reagent (depicted below the structure as Rg.), the following compounds were prepared.

Workup

  1. stirringThe mixture was stirred at room temperature for 18 hours
  2. customquenched with water and acetic acid (pH=4)
  3. extractionThe mixture was extracted with diethyl ether (3×)
  4. washThe combined organic phases were washed with water (3×)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash chromatography (ISCO, 0 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-7813cedc8dd448f889b1003928521bb2
Source dataset
uspto-grants-2016_05
Patent number
US09328138B2

Reaction notes

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