Water → HCID 57733992, compound

HRID 424766Notes

Reaction equation

HRID 424766 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:16]=[CH:15][C:14]3[C:13]([C:17]([NH:19][CH2:20][C:21]4([OH:28])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]4)=[O:18])=[C:12]([Cl:29])[CH:11]=[CH:10][C:9]=3[N:8]=2)[CH2:3]1.[CH3:30][C:31]([Si:34]([CH3:40])([CH3:39])[O:35][CH2:36][CH:37]=O)([CH3:33])[CH3:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>ClCCl>[Si:34]([O:35][CH2:36][CH2:37][NH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:16]=[CH:15][C:14]3[C:13]([C:17]([NH:19][CH2:20][C:21]4([OH:28])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]4)=[O:18])=[C:12]([Cl:29])[CH:11]=[CH:10][C:9]=3[N:8]=2)[CH2:3]1)([C:31]([CH3:33])([CH3:32])[CH3:30])([CH3:40])[CH3:39]

Participants

6

Reactant 4

HCID 962WaterHCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 577339902-[(3S)-3-Aminopyrrolidin-1-yl]-6-chloro-N-[(1-hydroxycycloheptyl)methyl]-quinoline-5-carboxamide

Product 1

HCID 57733992HCID 57733992, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-[(3S)-3-Aminopyrrolidin-1-yl]-6-chloro-N-[(1-hydroxycycloheptyl)methyl]-quinoline-5-carboxamide (17.6 g) was suspended in dichloromethane (300 ml) and molecular sieves (17.6 g) were added under a nitrogen atmosphere. [[(1,1-dimethylethyl)-dimethylsilyl]-oxy]acetaldehyde (7.2 ml) was added dropwise with stirring over 5 minutes and the mixture was stirred at room temperature for 6 hours. Sodium triacetoxyborohydride (17.9 g) was added in one portion and the mixture was stirred at room temperature for a further 17 hours before water (10 ml) was added, the mixture was stirred at room temperature for 30 minutes, concentrated onto silica in vacuo and purified by flash column chromatography (SiO2, 1:2:97-1:8:91 7M NH3 in methanol:methanol:dichloromethane as gradient elution) to afford the subtitle product as a colourless solid (16.0 g). Impure fractions (4.1 g) were repurified by flash column chromatography (SiO2, 1:2:97-1:8:91 7M NH3 in methanol:methanol:dichloromethane as gradient elution) to afford a second crop of the subtitle product (2.8 g).

Workup

  1. additionmolecular sieves (17.6 g) were added under a nitrogen atmosphere
  2. stirringthe mixture was stirred at room temperature for 6 hours
  3. additionwas added
  4. stirringthe mixture was stirred at room temperature for 30 minutes
  5. concentrationconcentrated onto silica in vacuo
  6. custompurified by flash column chromatography (SiO2, 1:2:97-1:8:91 7M NH3 in methanol:methanol:dichloromethane as gradient elution)

Sources & evidence

ORD record
ord-43be8ed82a9f4b04a23863c77e32edab
Source dataset
uspto-grants-2012_01
Patent number
US08106073B2

Reaction notes

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