Hydrochloric Acid → N-(4,4-dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-[(1H-pyrrolo[2,3-b]pyridin-4-ylmethyl)-amino]-nicotinamide

HRID 1815208Notes

Reaction equation

HRID 1815208 reaction equation
C(OC([N:8]1[CH2:17][C:16]([CH3:19])([CH3:18])[C:15]2[C:10](=[CH:11][C:12]([NH:20][C:21]([C:23]3[C:24]([NH:29][CH2:30][C:31]4[CH:36]=[CH:35][N:34]=[C:33]5[NH:37][CH:38]=[CH:39][C:32]=45)=[N:25][CH:26]=[CH:27][CH:28]=3)=[O:22])=[CH:13][CH:14]=2)[CH2:9]1)=O)(C)(C)C.Cl.C([O-])(O)=O.[Na+]>O1CCOCC1>[CH3:18][C:16]1([CH3:19])[C:15]2[C:10](=[CH:11][C:12]([NH:20][C:21](=[O:22])[C:23]3[CH:28]=[CH:27][CH:26]=[N:25][C:24]=3[NH:29][CH2:30][C:31]3[CH:36]=[CH:35][N:34]=[C:33]4[NH:37][CH:38]=[CH:39][C:32]=34)=[CH:13][CH:14]=2)[CH2:9][NH:8][CH2:17]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 600537294,4-dimethyl-7-({2-[(1H-pyrrolo[2,3-b]pyridin-4-ylmethyl)-amino]-pyridine-3-carbonyl}-amino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Product 1

HCID 10025493N-(4,4-dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-[(1H-pyrrolo[2,3-b]pyridin-4-ylmethyl)-amino]-nicotinamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 4,4-dimethyl-7-({2-[(1H-pyrrolo[2,3-b]pyridin-4-ylmethyl)-amino]-pyridine-3-carbonyl}-amino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (0.115 g, step A), HCl (4N, 3 mL) and dioxane (4 mL) was stirred at RT for overnight. Sat'd NaHCO3 was added until the bubbling stopped. The aqueous phase was extracted with EtOAc 3 times. The combined organic phases were dried over Na2SO4 and evaporated to yield a light purple oil as a crude product, which was purified by chromatography through silica gel (10 g, 5% MeOH/CHCl3 with 1% NH4OH) to afford N-(4,4-dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-[(1H-pyrrolo[2,3-b]pyridin-4-ylmethyl)-amino]-nicotinamide. The material was further purified via silica gel column chromatography (10 g, 1% to 5% MeOH/CH2Cl2, stepwise gradient) to afford pure title compound. MS: (ES+) 427 (M+H). Calc'd. for C25H26N6O—426.51.

Workup

  1. extractionThe aqueous phase was extracted with EtOAc 3 times
  2. dry with materialThe combined organic phases were dried over Na2SO4
  3. customevaporated
  4. customto yield a light purple oil as a crude product, which
  5. customwas purified by chromatography through silica gel (10 g, 5% MeOH/CHCl3 with 1% NH4OH)

Sources & evidence

ORD record
ord-952692823f274d23922efe1c9a3b7ce2
Source dataset
uspto-grants-2005_04
Patent number
US06878714B2

Reaction notes

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