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 730683Notes

Reaction equation

HRID 730683 reaction equation
[N:1]1([CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH2:6][CH2:5][CH:4]([O:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:3][CH2:2]1.[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:17]3[CH2:16][CH2:15][CH:14]([N:1]4[CH2:2][CH2:3][CH:4]([O:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:5][CH2:6]4)[CH2:19][CH2:18]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-f54f0b83a45243d08b2bd81748cee24d
Source dataset
uspto-grants-2009_09
Patent number
US07582625B2

Reaction notes

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