1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl 2-(4-(3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-oxoethylcarbamate

HRID 79608Notes

Reaction equation

HRID 79608 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[NH:13][CH:14]=[C:15]([NH:16][C:17](=[O:24])[C:18]4[CH:23]=[CH:22][CH:21]=[N:20][CH:19]=4)[C:8]=23)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:25]([O:29][C:30]([NH:32][CH2:33][C:34](O)=[O:35])=[O:31])([CH3:28])([CH3:27])[CH3:26].C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:17]([NH:16][C:15]1[C:8]2[C:9](=[N:10][CH:11]=[CH:12][C:7]=2[N:1]2[CH2:2][CH2:3][N:4]([C:34](=[O:35])[CH2:33][NH:32][C:30](=[O:31])[O:29][C:25]([CH3:26])([CH3:27])[CH3:28])[CH2:5][CH2:6]2)[NH:13][CH:14]=1)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[N:20][CH:19]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 68763236N-(4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide

Product 1

HCID 68780070tert-butyl 2-(4-(3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-oxoethylcarbamateYield 46.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Crude N-(4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyri din-3-yl)nicotinamide (0.025 g, 0.058 mmol, see Example 50), 2-(tert-butoxycarbonylamino)acetic acid (0.0111 g, 0.0637 mmol), HOBT-H2O (0.0124 g, 0.0811 mmol) and EDCI (0.0144 g, 0.075 mmol) were placed in DCM (3 mL). DIEA (d 0.742; 0.0504 mL, 0.290 mmol) was then added. The reaction was stirred for 2 hours and quenched with saturated Na2CO3. The mixture was then extracted with DCM. The organic fractions were dried, filtered, and concentrated to give a crude oil that was purified by column chromatography (500:20-500:30) to give tert-butyl 2-(4-(3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-oxoethylcarbamate (0.013 g, 46.8% yield).

Workup

  1. customquenched with saturated Na2CO3
  2. extractionThe mixture was then extracted with DCM
  3. customThe organic fractions were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude oil that
  7. customwas purified by column chromatography (500:20-500:30)

Sources & evidence

ORD record
ord-3ddee3c537654ed9869b8af0a00735c0
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

Loading…