Dimethylamine → N,N-dicyclopropyl-4-(5-(dimethylcarbamoyl)-1-ethyl-1H-pyrazol-3-ylamino)-6-ethyl-1-methyl-1,6-dihydro imidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

HRID 220404Notes

Reaction equation

HRID 220404 reaction equation
[CH:1]1([N:4]([CH:34]2[CH2:36][CH2:35]2)[C:5]([C:7]2[N:31]([CH2:32][CH3:33])[C:10]3=[N:11][C:12]([NH:19]/[C:20](/SC)=[CH:21]/[C:22](=O)[CH:23]([O:26]C)OC)=[C:13]4[N:17]=[CH:16][N:15]([CH3:18])[C:14]4=[C:9]3[CH:8]=2)=[O:6])[CH2:3][CH2:2]1.CN(C(O[N:45]1[N:53]=N[C:47]2C=CC=N[C:46]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:61][NH:62][CH3:63].O>CN(C=O)C>[CH:1]1([N:4]([CH:34]2[CH2:36][CH2:35]2)[C:5]([C:7]2[N:31]([CH2:32][CH3:33])[C:10]3=[N:11][C:12]([NH:19][C:20]4[CH:21]=[C:22]([C:23](=[O:26])[N:62]([CH3:63])[CH3:61])[N:45]([CH2:46][CH3:47])[N:53]=4)=[C:13]4[N:17]=[CH:16][N:15]([CH3:18])[C:14]4=[C:9]3[CH:8]=2)=[O:6])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 962WaterHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58180627(Z)-N,N-Dicyclopropyl-4-(4,4-dimethoxy-1-(methylthio)-3-oxobut-1-enylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

Product 1

HCID 58180621N,N-dicyclopropyl-4-(5-(dimethylcarbamoyl)-1-ethyl-1H-pyrazol-3-ylamino)-6-ethyl-1-methyl-1,6-dihydro imidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamideYield 67.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)-1-ethyl-1H-pyrazole-5-carboxylic acid (example 101, 28 mg, 0.059 mmol), HATU (26.8 mg, 0.071 mmol) and dimethylamine (2M in THF, 59 μL, 0.118 mmol) in DMF (1 mL) was stirred at room temperature for 2 h. Water was added and the reaction mixture was extracted with ethyl acetate 3 times. The combined organic layers were washed twice with 10% lithium chloride, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude was purified by preparative HPLC (Phenomenex Luna 5u C18 column, 21.2×250 mm column, retention time 15.317 min, 30-100% gradient aqueous methanol over 20 minutes containing 10 mM ammonium acetate, flow rate 20 ml/min and monitoring at 254 nm). N,N-dicyclopropyl-4-(5-(dimethylcarbamoyl)-1-ethyl-1H-pyrazol-3-ylamino)-6-ethyl-1-methyl-1,6-dihydro imidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (20 mg, 66.9% yield) was obtained as an off-white solid.

Workup

  1. extractionthe reaction mixture was extracted with ethyl acetate 3 times
  2. washThe combined organic layers were washed twice with 10% lithium chloride
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude was purified by preparative HPLC (Phenomenex Luna 5u C18 column, 21.2×250 mm column, retention time 15.317 min, 30-100% gradient aqueous methanol over 20 minutes containing 10 mM ammonium acetate, flow rate 20 ml/min and monitoring at 254 nm)

Sources & evidence

ORD record
ord-03679465959840609309cce02d8c591e
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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