Diisopropylethylamine → 5-Benzyloxy-2-(4,4-difluoro-piperidine-1-carbonyl)-pyrrolo[2,3-b]pyridine-1-carboxylic Acid tert-butyl Ester

HRID 1437698Notes

Reaction equation

HRID 1437698 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]2=[N:13][CH:14]=[C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:16]=[C:11]2[CH:10]=[C:9]1[C:25](O)=[O:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl.[F:51][C:52]1([F:58])[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1.C(N(CC)C(C)C)(C)C.C(=O)(O)[O-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[C:12]2=[N:13][CH:14]=[C:15]([O:17][CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:16]=[C:11]2[CH:10]=[C:9]1[C:25]([N:55]1[CH2:56][CH2:57][C:52]([F:58])([F:51])[CH2:53][CH2:54]1)=[O:26])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27583514,4-Difluoropiperidine hydrochlorideHCID 684251515-Benzyloxy-pyrrolo[2,3-b]pyridine-1,2-dicarboxylic acid 1-tert-butyl ester2×

Product 1

HCID 684261195-Benzyloxy-2-(4,4-difluoro-piperidine-1-carbonyl)-pyrrolo[2,3-b]pyridine-1-carboxylic Acid tert-butyl EsterYield 95.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the solution of 2.3 g (6.2 mmol) 5-benzyloxy-pyrrolo[2,3-b]pyridine-1,2-dicarboxylic acid 1-tert-butyl ester (intermediate G), 2.5 g (7.8 mmol) O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate and 1.2 g (7.8 mmol) 4,4-difluoropiperidine hydrochloride in 30 ml DMF, 6.4 ml (4.8 g, 37.4 mmol) N,N-diisopropylethylamine were added. After 40 min. stirring at room temperature the clear solution was poured on saturated aqueous sodium bicarbonate solution and was extracted three times with ethyl acetate. The combined organic layers were washed three times with water and with brine, dried over magnesium sulfate, filtered and evaporated. The residue was re-crystallized from dichloromethane and n-heptane to give 2.8 g (95%) of the desired compound as a colorless solid.

Workup

  1. extractionwas extracted three times with ethyl acetate
  2. washThe combined organic layers were washed three times with water
  3. dry with materialwith brine, dried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was re-crystallized from dichloromethane and n-heptane

Sources & evidence

ORD record
ord-871f6431ed39457ebeb14cb1290fb053
Source dataset
uspto-grants-2009_11
Patent number
US07622466B2

Reaction notes

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