2-(Methylamino)ethanol → (e)-3-(5-Cyano-2-methoxy-phenyl)-n-((r)-2-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-1-{[(2-hydroxy-ethyl)-methyl-carbamoyl]-methyl}-ethyl)-acrylamide

HRID 1797266Notes

Reaction equation

HRID 1797266 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:34][CH3:35])=[C:7](/[CH:9]=[CH:10]/[C:11]([NH:13][C@@H:14]([CH2:19][N:20]2[CH2:25][CH2:24][CH:23]([O:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[CH2:22][CH2:21]2)[CH2:15][C:16](O)=[O:17])=[O:12])[CH:8]=1)#[N:2].C(N(C(C)C)CC)(C)C.[CH3:45][NH:46][CH2:47][CH2:48][OH:49].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C([O-])(O)=O.[Na+].FC1C=CC(OC2CCN(C[C@@H](C(=C)C(N)=O)CC(=O)N(CCO)C)CC2)=CC=1>CN(C=O)C.C(OC(=O)C)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:34][CH3:35])=[C:7](/[CH:9]=[CH:10]/[C:11]([NH:13][C@H:14]([CH2:15][C:16](=[O:17])[N:46]([CH2:47][CH2:48][OH:49])[CH3:45])[CH2:19][N:20]2[CH2:21][CH2:22][CH:23]([O:26][C:27]3[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=3)[CH2:24][CH2:25]2)=[O:12])[CH:8]=1)#[N:2]

Participants

9

Reactant 6

HCID 80162-(Methylamino)ethanolHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10140715(R)-3-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-4-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-butyric acidHCID 131725718((R)-2-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-1-{[(2-hydroxy-ethyl)-methyl-carbamoyl]-methyl}-ethyl)-acrylamide

Product 1

HCID 10280381(e)-3-(5-Cyano-2-methoxy-phenyl)-n-((r)-2-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-1-{[(2-hydroxy-ethyl)-methyl-carbamoyl]-methyl}-ethyl)-acrylamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (R)-3-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-4-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-butyric acid (0.1 g, 0.21 mmol) in DMF (1 ml) is treated with diisopropylethylamine (0.108 ml, 0.62 mmol) and 2-methylamino-ethanol (0.02 ml, 0.248 mmol). To the solution is added O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (0.117 g, 0.31 mmol) and the reaction mixture stirred at room temperature for 1 hour. The reaction mixture is partioned between ethylacetate and saturated aqueous NaHCO3. The ethylacetate phase is washed with saturated brine, dried over MgSO4 and evaporated. The crude product is purified by flash silica chromatography (elution with 5:95 methanol/DCM) to afford (E)-3-(5-cyano-2-methoxy-phenyl)-.N.-((R)-2-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-1-{[(2-hydroxy-ethyl)-methyl-carbamoyl]-methyl}-ethyl)-acrylamide. [M-H] 537.02.

Workup

  1. washThe ethylacetate phase is washed with saturated brine
  2. dry with materialdried over MgSO4
  3. customevaporated
  4. customThe crude product is purified by flash silica chromatography (elution with 5:95 methanol/DCM)
  5. customto afford (E)-3-(5-cyano-2-methoxy-phenyl)-.N

Sources & evidence

ORD record
ord-07441c7880a84acc94db9249f453d3ac
Source dataset
uspto-grants-2006_04
Patent number
US07034042B2

Reaction notes

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