Tetrahydrofuran → Ethyl [({[1-({[(3R)-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]amino}carbonyl)piperidin-4-yl]amino}carbonyl)amino](pyridin-2-yl)acetate

HRID 1867622Notes

Reaction equation

HRID 1867622 reaction equation
[NH2:1][C@@H:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]([CH2:19][C:20]([F:23])([F:22])[F:21])[C:3]1=[O:24].C(N(CC)CC)C.[NH:32]1[CH2:37][CH2:36][CH:35]([NH:38][C:39]([NH:41][CH:42]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][N:49]=2)[C:43]([O:45][CH2:46][CH3:47])=[O:44])=[O:40])[CH2:34][CH2:33]1.[O:54]1CCC[CH2:55]1>CN(C)C=O>[O:24]=[C:3]1[C@H:2]([NH:1][C:55]([N:32]2[CH2:37][CH2:36][CH:35]([NH:38][C:39]([NH:41][CH:42]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][N:49]=3)[C:43]([O:45][CH2:46][CH3:47])=[O:44])=[O:40])[CH2:34][CH2:33]2)=[O:54])[N:8]=[C:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]1[CH2:19][C:20]([F:21])([F:23])[F:22]

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 8471Triethylamine2×HCID 10854086HCID 10854086, compoundHCID 86620352Ethyl {[(piperidin-4-ylamino)carbonyl]amino}(pyridin-2-yl)acetate

Product 1

HCID 86620351Ethyl [({[1-({[(3R)-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]amino}carbonyl)piperidin-4-yl]amino}carbonyl)amino](pyridin-2-yl)acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(3R)-3-Amino-5-phenyl-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (90 mg, 0.270 mmol) (Y.-J. Shi et al., Tetrahedron, 1999, 55, 909-918) and triethylamine (37 uL, 0.270 mmol) in tetrahydrofuran (3 mL) were added to a solution of p-nitrophenylchloroformate (54 mg, 0.270 mmol) in tetrahydrofuran (15 mL) at 0° C. After 1 h, additional triethylamine (74 uL, 0.540 mmol) and ethyl {[(piperidin-4-ylamino)carbonyl]amino}(pyridin-2-yl)acetate (100 mg, 0.598 mmol) in tetrahydrofuran (5 μL) and dimethyl formamide (1 mL) were added and stirred at 0 oC for 10 min and then warmed to room temperature. After 4 h, the reaction was concentrated and the residue dissolved in ethyl acetate, washed with 1 N sodium hydroxide solution (3×), water, brine, and dried over magnesium sulfate. Purification by silica gel chromatography (100% dichloromethane→12% methanol/dichloromethane) gave 70 mg of the titled compound.

Workup

  1. waitAfter 4 h
  2. concentrationthe reaction was concentrated
  3. dissolutionthe residue dissolved in ethyl acetate
  4. washwashed with 1 N sodium hydroxide solution (3×), water, brine
  5. dry with materialdried over magnesium sulfate
  6. customPurification by silica gel chromatography (100% dichloromethane→12% methanol/dichloromethane)

Sources & evidence

ORD record
ord-b93f7f07c4474c13a12dfe87ea210925
Source dataset
uspto-grants-2009_12
Patent number
US07632832B2

Reaction notes

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