2,6-Lutidine → HCID 58180616, compound

HRID 220386Notes

Reaction equation

HRID 220386 reaction equation
[CH:1]1([N:4]([CH:33]2[CH2:35][CH2:34]2)[C:5]([C:7]2[N:30]([CH2:31][CH3:32])[C:10]3=[N:11][C:12]([NH:19][C:20]4[S:21][C:22]([C:27]([OH:29])=O)=[C:23]([CH2:25][CH3:26])[N:24]=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.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1C(C)=CC=CC=1C.[NH:68]1[CH2:73][CH2:72][S:71](=[O:75])(=[O:74])[CH2:70][CH2:69]1>C(Cl)Cl.CN(C=O)C>[CH:1]1([N:4]([CH:33]2[CH2:35][CH2:34]2)[C:5]([C:7]2[N:30]([CH2:31][CH3:32])[C:10]3=[N:11][C:12]([NH:19][C:20]4[S:21][C:22]([C:27]([N:68]5[CH2:73][CH2:72][S:71](=[O:75])(=[O:74])[CH2:70][CH2:69]5)=[O:29])=[C:23]([CH2:25][CH3:26])[N:24]=4)=[C:13]4[N:17]=[CH:16][N:15]([CH3:18])[C:14]4=[C:9]3[CH:8]=2)=[O:6])[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 6484228Thiomorpholine 1,1-dioxideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58180624HCID 58180624, compound

Product 1

HCID 58180616HCID 58180616, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 2-(7-(dicyclopropylcarbamoyl)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-ylamino)-4-ethylthiazole-5-carboxylic acid (example 69B, 33 mg, 0.067 mmol), HATU (50.8 mg, 0.134 mmol), 2,6-lutidine (0.020 mL, 0.174 mmol), and DMF (1 mL) was added thiomorpholine 1,1-dioxide (27.1 mg, 0.201 mmol). The solution was then stirred at 50° C. for 1.5 hrs. The reaction was then cooled to room temperature and diluted with methylene chloride. The solution was then washed with saturated aqueous sodium bicarbonate, 10% LiCl in H2O, and saturated aqueous sodium bicarbonate again. The organic phase was dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude residue was then purified by silica-gel flash chromatography using an Isco 40 g column eluting from 0-6% MeOH/CH2Cl2 to give N,N-dicyclopropyl-6-ethyl-4-(4-ethyl-5-(1,1-dioxothiomorpholine-4-carbonyl)thiazol-2-ylamino)-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (21.7 mg, 52.6% yield) as a pale yellow solid.

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. washThe solution was then washed with saturated aqueous sodium bicarbonate, 10% LiCl in H2O, and saturated aqueous sodium bicarbonate again
  3. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude residue was then purified by silica-gel flash chromatography
  6. washeluting from 0-6% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-f26809ab0f8b40b49806cbd59d125fb9
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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