1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl 3-((5-(3-(2-(tert-butyldimethylsilyloxy)ethylcarbamoyl)-1H-pyrrol-1-yl)-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate

HRID 384668Notes

Reaction equation

HRID 384668 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][NH:15][C:16]2[CH:21]=[C:20]([NH:22][C:23]3[CH:28]=[N:27][C:26]([C:29]#[N:30])=[CH:25][N:24]=3)[N:19]=[CH:18][C:17]=2[N:31]2[CH:35]=[CH:34][C:33]([C:36](O)=[O:37])=[CH:32]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Si:39]([O:46][CH2:47][CH2:48][NH2:49])([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40].C(N(C(C)C)C(C)C)C.O.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC>CN(C=O)C>[Si:39]([O:46][CH2:47][CH2:48][NH:49][C:36]([C:33]1[CH:34]=[CH:35][N:31]([C:17]2[C:16]([NH:15][CH2:14][CH:10]3[CH2:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]3)=[CH:21][C:20]([NH:22][C:23]3[CH:28]=[N:27][C:26]([C:29]#[N:30])=[CH:25][N:24]=3)=[N:19][CH:18]=2)[CH:32]=1)=[O:37])([C:42]([CH3:44])([CH3:45])[CH3:43])([CH3:41])[CH3:40]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 529218(2-Aminoethoxy)(tert-butyl)dimethylsilaneHCID 27960291-Hydroxybenzotriazole hydrateHCID 667465061-(4-((1-(tert-Butoxycarbonyl)piperidin-3-yl)methylamino)-6-(5-cyanopyrazin-2-ylamino)pyridin-3-yl)-1H-pyrrole-3-carboxylic acid

Product 1

HCID 66745676tert-butyl 3-((5-(3-(2-(tert-butyldimethylsilyloxy)ethylcarbamoyl)-1H-pyrrol-1-yl)-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(4-((1-(tert-Butoxycarbonyl)piperidin-3-yl)methylamino)-6-(5-cyanopyrazin-2-ylamino)pyridin-3-yl)-1H-pyrrole-3-carboxylic acid (80 mg, 0.154 mmol) was dissolved in DMF (1.5 mL). 2-(tert-Butyldimethylsilyloxy)ethanamine (41 mg, 0.230 mmol), N-ethyldiisopropylamine (30 mg, 0.230 mmol), 1-hydroxy benzotriazole hydrate (31 mg, 0.230 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (44 mg, 0.23 mmol) were added to the solution and the reaction mixture was stirred for 14 h at room temperature. The solution was partitioned between dichloromethane and water. The two phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried (Na2SO4) and evaporated to give tert-butyl 3-((5-(3-(2-(tert-butyldimethylsilyloxy)ethylcarbamoyl)-1H-pyrrol-1-yl)-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate (80 mg, 78%) which was used in the next step without purification.

Workup

  1. customThe solution was partitioned between dichloromethane and water
  2. customThe two phases were separated
  3. extractionthe aqueous phase was extracted with dichloromethane
  4. dry with materialThe combined organic phases were dried (Na2SO4)
  5. customevaporated

Sources & evidence

ORD record
ord-5700995f5c1b4ced9f95486ce6ac0911
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

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