Acetic Acid → (R)-1-(4-hydroxy-3,5-dimethyl-benzyl)-2-(4-hydroxy-4-methyl-[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 1015484Notes

Reaction equation

HRID 1015484 reaction equation
[O:1]=[C:2]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C@H:18]([CH2:28][C:29]3[CH:34]=[C:33]([CH3:35])[C:32]([OH:36])=[C:31]([CH3:37])[CH:30]=3)[C:19](=[O:27])[N:20]3[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]3)=[O:16])[CH2:11][CH2:10]2)[CH2:7][CH2:6][C:5]2[CH:38]=[CH:39][CH:40]=[CH:41][C:4]=2[NH:3]1.[CH3:42][C:43]1([OH:49])[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1.CC(O)=O.[Na].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C>C(Cl)Cl.CN(C=O)C>[O:1]=[C:2]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C@H:18]([CH2:28][C:29]3[CH:34]=[C:33]([CH3:35])[C:32]([OH:36])=[C:31]([CH3:37])[CH:30]=3)[C:19]([N:20]3[CH2:21][CH2:22][CH:23]([N:46]4[CH2:47][CH2:48][C:43]([OH:49])([CH3:42])[CH2:44][CH2:45]4)[CH2:24][CH2:25]3)=[O:27])=[O:16])[CH2:11][CH2:10]2)[CH2:7][CH2:6][C:5]2[CH:38]=[CH:39][CH:40]=[CH:41][C:4]=2[NH:3]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 156491744-Methylpiperidin-4-olHCID 67302216(R)-1-(4-hydroxy-3,5-dimethyl-benzyl)-2-oxo-2-(4-oxo-piperidin-1-yl)-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylateHCID 131725371CID 131725371

Product 1

HCID 57529630(R)-1-(4-hydroxy-3,5-dimethyl-benzyl)-2-(4-hydroxy-4-methyl-[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 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 50 mg (0.09 mmol) of (R)-1-(4-hydroxy-3,5-dimethyl-benzyl)-2-oxo-2-(4-oxo-piperidin-1-yl)-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate (Example 79) in 1.5 mL DCM was combined with 21 mg (0.18 mmol) 4-methyl-piperidin-4-ol and 10.3 μl (0.19 mmol) AcOH, cooled to 0° C. and stirred for 2 h. Then 28 mg (0.19 mmol) sodium-triacetoxyborohydride were added and the mixture was stirred overnight at 0° C. After the solvent had been eliminated the residue was combined with 2 mL DMF and purified by HPLC. The fractions containing the product were combined and lyophilised.

Workup

  1. stirringthe mixture was stirred overnight at 0° C
  2. custompurified by HPLC
  3. additionThe fractions containing the product

Sources & evidence

ORD record
ord-a3aaca25fae64c51add924bcf1b11b69
Source dataset
uspto-grants-2011_07
Patent number
US07985747B2

Reaction notes

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