1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-tert-Butyl 3-methyl-1-(4-(3-(nicotinamido)-1H-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-1-oxobutan-2-ylcarbamate

HRID 79609Notes

Reaction equation

HRID 79609 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][C@H:33]([CH:37]([CH3:39])[CH3:38])[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>[CH3:38][CH:37]([CH3:39])[C@@H:33]([NH:32][C:30](=[O:31])[O:29][C:25]([CH3:28])([CH3:27])[CH3:26])[C:34]([N:4]1[CH2:3][CH2:2][N: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]1)=[O:35]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 637605(2R)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 68763236N-(4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide

Product 1

HCID 68784483(R)-tert-Butyl 3-methyl-1-(4-(3-(nicotinamido)-1H-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-1-oxobutan-2-ylcarbamateYield 29.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide (0.025 g, 0.058 mmol, see Example 50), (R)-2-(tert-butoxycarbonylamino)-3-methylbutanoic acid (0.0138 g, 0.0637 mmol), HOBT-H2O (0.0124 g, 0.0811 mmol) and EDCI (0.0144 g, 0.0752 mmol) were placed in DCM (3 mL). DIEA (d 0.742; 0.0504 mL, 0.290 mmol) was then added, and the reaction was stirred for 2 hours. The reaction was 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 (500:20-500:28) to give (R)-tert-butyl 3-methyl-1-(4-(3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-1-oxobutan-2-ylcarbamate (0.009 g, 29.7% yield).

Workup

  1. customThe reaction was quenched 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 (500:20-500:28)

Sources & evidence

ORD record
ord-3fd50fee8ccf4d7caa8743f89beb5d7c
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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