4-Methylmorpholine → HCID 59212019, compound

HRID 655191Notes

Reaction equation

HRID 655191 reaction equation
C(N=C=NCCCN(C)C)C.[C:12]([O:16][C:17]([NH:19][C@H:20]1[CH2:24][CH2:23][N:22]([C:25](=[O:45])[CH2:26][N:27]([CH2:41][C:42]([OH:44])=O)[C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[CH:30][CH:29]=2)[CH2:21]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].ON1C2N=CC=CC=2N=N1.[Cl:56][C:57]1[CH:58]=[C:59]([CH:62]=[CH:63][CH:64]=1)[CH2:60][NH2:61].CN1CCOCC1>CN(C=O)C.C(OCC)(=O)C>[Cl:56][C:57]1[CH:58]=[C:59]([CH:62]=[CH:63][CH:64]=1)[CH2:60][NH:61][C:42]([CH2:41][N:27]([C:28]1[CH:29]=[CH:30][C:31]([O:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)=[CH:32][CH:33]=1)[CH2:26][C:25]([N:22]1[CH2:23][CH2:24][C@H:20]([NH:19][C:17](=[O:18])[O:16][C:12]([CH3:15])([CH3:13])[CH3:14])[CH2:21]1)=[O:45])=[O:44]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 77802Benzenemethanamine, 3-chloro-HCID 181649HOAtHCID 59211952HCID 59211952, compound

Product 1

HCID 59212019HCID 59212019, compoundYield 72.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide (144 mg, 0.75 mmol) was added to a solution of [[2-((S)-3-tert-butoxycarbonylaminopyrrolidin-1-yl)-2-oxo-ethyl]-(4-phenoxyphenyl)amino]acetic acid 20 (176 mg, 0.37 mmol), 1-hydroxy-7-azabenzotriazole (103 mg, 0.76 mmol), 3-chlorobenzylamine (0.092 mL, 0.76 mmol) and N-methylmorpholine (0.11 mL, 1.02 mmol) in DMF (5 mL). The reaction mixture was stirred overnight at room temperature and then diluted with ethyl acetate and washed with 10% hydrochloric acid (×2), brine, saturated aqueous sodium bicarbonate (×2) and then brine, dried (Na2SO4) and evaporated onto silica gel. Flash column chromatography, using ethyl acetate as the eluent, gave the title compound as a hard foam (159 mg, 71%). 1HNMR (300 MHz) (CDCl3) δ 1.45 (6H, s), 1.55 (3H, s), 1.8-2.4 (2H, m), 3.35-3.90 (5H, m), 3.95-4.40 (4H, m), 4.55-4.70 (2H, m), 6.48 (2H, m), 6.75-7.05 (6H, m), 7.12 (3H, m), 7.25 (2H, m) and 9.81 (1H, m).

Workup

  1. washwashed with 10% hydrochloric acid (×2), brine, saturated aqueous sodium bicarbonate (×2)
  2. dry with materialbrine, dried (Na2SO4)
  3. customevaporated onto silica gel

Sources & evidence

ORD record
ord-fb44b60cfb4242c1b0b408ec0570c597
Source dataset
uspto-grants-2011_12
Patent number
US08071582B2

Reaction notes

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