Cyano-borohydride → (R)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-((1-(2-morpholinoethyl)pyrrolidin-3-yl)methyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 2061827Notes

Reaction equation

HRID 2061827 reaction equation
[CH2:1]([NH:3][C:4](=[O:43])[NH:5][C:6]1[N:11]=[CH:10][C:9]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[N:18]([CH2:22][C@@H:23]2[CH2:27][CH2:26][NH:25][CH2:24]2)[CH:17]=[C:16]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:15]3=[O:33])=[C:8]([C:34]2[S:35][CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[N:38]=2)[CH:7]=1)[CH3:2].Cl.O.[N:46]1([CH2:52][CH:53]=O)[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1.C([BH3-])#N>CO>[CH2:1]([NH:3][C:4](=[O:43])[NH:5][C:6]1[N:11]=[CH:10][C:9]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[N:18]([CH2:22][C@@H:23]2[CH2:27][CH2:26][N:25]([CH2:53][CH2:52][N:46]4[CH2:51][CH2:50][O:49][CH2:48][CH2:47]4)[CH2:24]2)[CH:17]=[C:16]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:15]3=[O:33])=[C:8]([C:34]2[S:35][CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[N:38]=2)[CH:7]=1)[CH3:2]

Participants

5

Reactant 3

HCID 498716Cyano-borohydrideHCID 17998884Morpholin-4-yl-acetaldehyde monohydrate hydrochlorideHCID 86643625(R)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-4-oxo-1-(pyrrolidin-3-ylmethyl)-1,4-dihydroquinoline-3-carboxylate

Product 1

HCID 86643628(R)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-((1-(2-morpholinoethyl)pyrrolidin-3-yl)methyl)-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 38.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A vial was charged with (R)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-4-oxo-1-(pyrrolidin-3-ylmethyl)-1,4-dihydroquinoline-3-carboxylate (Example 233, 700 mg, 1.14 mmol) and morpholin-4-yl-acetaldehyde monohydrate hydrochloride (250 mg, 1.37 mmol) in methanol (10 mL). MP-cyanoborohydride (730 mg, 1.71 mmol) beads were added and the resulting mixture was allowed to stir at room temperature overnight. The reaction mixture was filtered and the beads were washed with more methanol. The filtrate was concentrated under reduced pressure and purified by Analogix SF15-24 g in dichloromethane/methanol system to give a light yellow solid (320 mg, 38.6%).

Workup

  1. filtrationThe reaction mixture was filtered
  2. washthe beads were washed with more methanol
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. custompurified by Analogix SF15-24 g in dichloromethane/methanol system

Sources & evidence

ORD record
ord-96633a2bd7854b7892314453fea9c441
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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