Triethylamine → (R)-1-(4-benzyloxy-3,5-dimethyl-benzyl)-2-(4-ethoxycarbonyl methoxy-1,4'-bipiperidinyl-1'-yl)-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 599778Notes

Reaction equation

HRID 599778 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[CH2:5][O:6][CH:7]1[CH2:12][CH2:11][N:10]([CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[CH2:9][CH2:8]1)[CH3:2].[O:20]=[C:21]1[N:27]([CH:28]2[CH2:33][CH2:32][N:31]([C:34]([O:36][C@@H:37]([C:55](O)=[O:56])[CH2:38][C:39]3[CH:44]=[C:43]([CH3:45])[C:42]([O:46][CH2:47][C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)=[C:41]([CH3:54])[CH:40]=3)=[O:35])[CH2:30][CH2:29]2)[CH2:26][CH2:25][C:24]2[CH:58]=[CH:59][CH:60]=[CH:61][C:23]=2[NH:22]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CN(C=O)C>[O:20]=[C:21]1[N:27]([CH:28]2[CH2:33][CH2:32][N:31]([C:34]([O:36][C@H:37]([CH2:38][C:39]3[CH:44]=[C:43]([CH3:45])[C:42]([O:46][CH2:47][C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)=[C:41]([CH3:54])[CH:40]=3)[C:55]([N:16]3[CH2:15][CH2:14][CH:13]([N:10]4[CH2:9][CH2:8][CH:7]([O:6][CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:19])[CH2:12][CH2:11]4)[CH2:18][CH2:17]3)=[O:56])=[O:35])[CH2:30][CH2:29]2)[CH2:26][CH2:25][C:24]2[CH:58]=[CH:59][CH:60]=[CH:61][C:23]=2[NH:22]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 25208036(R)-2-(4-benzyloxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylateHCID 57807779Ethyl([1,4']bipiperidinyl-4-yloxy)-acetate

Product 1

HCID 67273321(R)-1-(4-benzyloxy-3,5-dimethyl-benzyl)-2-(4-ethoxycarbonyl methoxy-1,4'-bipiperidinyl-1'-yl)-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

220 mg (0.64 mmol) ethyl([1,4′]bipiperidinyl-4-yloxy)-acetate (used as the bis-hydrochloride salt) were added at RT to a solution of 330 mg (0.58 mmol) (R)-2-(4-benzyloxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate (Example 1g), 200 mg (0.62 mmol) TBTU and 0.30 mL (2.16 mmol) triethylamine in 3 mL DMF and the mixture was stirred for 4 h. The reaction mixture was combined with saturated NaHCO3 solution while cooling with ice and the precipitate was suction filtered. This was dissolved in a little DCM and EtOH and purified by HPLC; the fractions containing the product were combined and lyophilised.

Workup

  1. temperaturewhile cooling with ice
  2. filtrationfiltered
  3. dissolutionThis was dissolved in a little DCM and EtOH
  4. custompurified by HPLC
  5. additionthe fractions containing the product

Sources & evidence

ORD record
ord-52ee849382a44ff0adf1ff59046ca2db
Source dataset
uspto-grants-2011_03
Patent number
US07897603B2

Reaction notes

Loading…