4-Methylmorpholine → HCID 67681760, compound

HRID 1751334Notes

Reaction equation

HRID 1751334 reaction equation
[NH2:1][C@H:2]([C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[C:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[C:23]4[C:28](=[CH:29][CH:30]=3)[CH:27]=[C:26]([C:31]3[NH:35][C:34]([C@@H:36]5[CH2:40][CH2:39][CH2:38][N:37]5[C:41](=[O:51])[C@@H:42]([NH:46][C:47](=[O:50])[O:48][CH3:49])[CH:43]([CH3:45])[CH3:44])=[N:33][CH:32]=3)[CH:25]=[CH:24]4)=[CH:17][CH:16]=2)=[CH:13][N:14]=1)=[O:4].[O:58]1[CH2:62][CH2:61][CH2:60][C@H:59]1[C:63](O)=[O:64].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[CH3:45][CH:43]([CH3:44])[C@H:42]([NH:46][C:47](=[O:50])[O:48][CH3:49])[C:41](=[O:51])[N:37]1[CH2:38][CH2:39][CH2:40][C@H:36]1[C:34]1[NH:35][C:31]([C:26]2[CH:25]=[CH:24][C:23]3[C:28](=[CH:29][CH:30]=[C:21]([C:18]4[CH:17]=[CH:16][C:15]([C:12]5[NH:11][C:10]([C@@H:6]6[CH2:7][CH2:8][CH2:9][N:5]6[C:3](=[O:4])[C@@H:2]([C:52]6[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=6)[NH:1][C:63]([C@H:59]6[CH2:60][CH2:61][CH2:62][O:58]6)=[O:64])=[N:14][CH:13]=5)=[CH:20][CH:19]=4)[CH:22]=3)[CH:27]=2)=[CH:32][N:33]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 446666Tetrahydro-2-furoic acid, (-)-HCID 2724699PyBOPHCID 67681858HCID 67681858, compound

Product 1

HCID 67681760HCID 67681760, compoundYield 13.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 0° C. solution of methyl (S)-1-((S)-2-(5-(6-(4-(2-((S)-1-((R)-2-amino-2-phenylacetyl) pyrrolidin-2-yl)-1H-imidazol-5-yl)phenyl)naphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (70 mg, 0.08 mmol) in DMF (1 mL) was added (S)-tetrahydrofuran-2-carboxylic acid (10 mg, 0.09 mmol), PyBOP (52 mg, 0.10 mmol), HOBT (14 mg, 0.10 mmol), and N-methylmorpholine (40 mg, 0.4 mmol) successively. The solution was warmed to rt and allowed to stir for 2 h. The mixture was diluted with EtOAc, washed with 1N HCl, sat. NaHCO3, and brine, dried over MgSO4, and concentrated. The residue was purified by silica gel chromatography to yield product (9.5 mg). LCMS-ESI+: calc'd for C50H54N8O6: 863.01 (M+); Found: 863.31 (M+H+).

Workup

  1. washwashed with 1N HCl, sat. NaHCO3, and brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f56368caf30d4b17a75c0ae3672d065a
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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