Piperidin-4-ol → [2-[5-(4-hydroxy-piperidine-1-carbonyl)-thiophen-2-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-(1-methyl-cyclohexyl)-methanone

HRID 547483Notes

Reaction equation

HRID 547483 reaction equation
[CH3:1][C:2]1([C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[S:23][C:22]([C:24](O)=[O:25])=[CH:21][CH:20]=4)[N:17]=3)[N:12]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:11]=2)=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[OH:62][CH:63]1[CH2:68][CH2:67][NH:66][CH2:65][CH2:64]1>CN(C)C=O.C(OCC)(=O)C>[OH:62][CH:63]1[CH2:68][CH2:67][N:66]([C:24]([C:22]2[S:23][C:19]([C:16]3[N:17]=[C:18]4[C:10]([C:8]([C:2]5([CH3:1])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]5)=[O:9])=[CH:11][N:12]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:33])([CH3:34])[CH3:32])[C:13]4=[N:14][CH:15]=3)=[CH:20][CH:21]=2)=[O:25])[CH2:65][CH2:64]1

Participants

6

Reactant 3

HCID 79341Piperidin-4-olHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 578295975-[7-(1-methyl-cyclohexanecarbonyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-thiophene-2-carboxylic acid

Product 1

HCID 57829606[2-[5-(4-hydroxy-piperidine-1-carbonyl)-thiophen-2-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-(1-methyl-cyclohexyl)-methanoneYield 34.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 5-[7-(1-methyl-cyclohexanecarbonyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-thiophene-2-carboxylic acid (0.080 g, 0.16 mmol), BOP (0.071 g, 0.16 mmol) and 4-hydroxypiperidine (0.162 g, 1.6 mmol) in 2 mL of N,N-dimethylformamide was stirred overnight. The resulting black mixture was taken up in 30 mL of ethyl acetate and washed with three 20 mL portions of a sat. aq. NH4Cl solution, dried over MgSO4, filtered and concentrated to a residue. Column chromatography (0->50% EtOAc/hexanes afforded 0.032 g (34%) of [2-[5-(4-hydroxy-piperidine-1-carbonyl)-thiophen-2-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-(1-methyl-cyclohexyl)-methanone as a tan oil.

Workup

  1. washwashed with three 20 mL portions of a sat. aq. NH4Cl solution
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-4c466415c3104375bae2f213829eb7c4
Source dataset
uspto-grants-2011_05
Patent number
US07939531B2

Reaction notes

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