Diisopropylethylamine → HCID 66744719, compound

HRID 1959483Notes

Reaction equation

HRID 1959483 reaction equation
[C:1]([O:5][C:6]([N:8]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C:9]1[N:10]=[CH:11][C:12]([CH:36]2[CH2:38][CH:37]2[C:39]([OH:41])=O)=[N:13][C:14]=1[C:15]1[O:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][N:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH3:28])=[CH:22][CH:21]=2)=[N:18][N:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:49]1[CH2:53][CH2:52][C@@H:51]([NH:54][C:55](=[O:61])[O:56][C:57]([CH3:60])([CH3:59])[CH3:58])[CH2:50]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[C:45]([O:44][C:42]([N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[C:9]1[C:14]([C:15]2[O:16][C:17]([C:20]3[CH:25]=[CH:24][C:23]([CH2:26][N:27]([CH3:28])[C:29](=[O:30])[O:31][C:32]([CH3:33])([CH3:34])[CH3:35])=[CH:22][CH:21]=3)=[N:18][N:19]=2)=[N:13][C:12]([CH:36]2[CH2:38][CH:37]2[C:39]([N:49]2[CH2:53][CH2:52][C@@H:51]([NH:54][C:55]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:61])[CH2:50]2)=[O:41])=[CH:11][N:10]=1)=[O:43])([CH3:48])([CH3:46])[CH3:47]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1514397(3R)-(+)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66744596HCID 66744596, compound

Product 1

HCID 66744719HCID 66744719, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-[5-[bis(tert-butoxycarbonyl)amino]-6-[5-[4-[[tert-butoxycarbonyl(methyl)amino]methyl]phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]cyclopropanecarboxylic acid (100 mg, 0.15 mmol) and tert-butyl N-[(3R)-pyrrolidin-3-yl]carbamate (31 mg, 0.17 mmol) in DMF (0.6 mL) at room temperature was added HATU (57 mg, 0.15 mmol) followed by the addition of DIEA (48 mg, 65 μL, 0.37 mmol) and reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with EtOAc and washed with 1M HCl solution, and then with brine. The layers were separated and the organic layer was dried over Na2SO4, filtered and concentrated to obtain tert-butyl N-[[4-[5-[3-[bis(tert-butoxycarbonyl)amino]-6-[2-[(3R)-3-(tert-butoxycarbonylamino)pyrrolidine-1-carbonyl]cyclopropyl]pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-methyl-carbamate, which was dissolved in of 50% TFA-DCM (1 mL) mixture and stirred for 25 minutes at room temperature. The reaction mixture was concentrated under reduced pressure. The crude material was dissolved in DMSO (1 mL), filtered and purified using reverse phase HPLC (10 to 99% MeOH in H2O with HCl modifier) to obtain [2-[5-amino-6-[5-[4-(methylaminomethyl)phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]cyclopropyl]-[(3R)-3-aminopyrrolidin-1-yl]methanone.

Workup

  1. washwashed with 1M HCl solution
  2. customThe layers were separated
  3. dry with materialthe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-631ca1d070924403a9444791ef346cb5
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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