Water → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-cyanomethyl-cyclopentyl)-amide

HRID 245918

Reaction equation

HRID 245918 reaction equation
C([N:4](CC)[CH:5]([CH3:7])[CH3:6])(C)C.[F:10][C:11]1[CH:19]=[C:18]2[C:14]([C:15]([C:21]3[N:22]=[C:23]4[C:29]([C:30]([OH:32])=O)=[CH:28][N:27]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[C:24]4=[N:25][CH:26]=3)=[N:16][N:17]2[CH3:20])=[CH:13][CH:12]=1.CN(C(O[N:49]1N=N[C:51]2[CH:52]=[CH:53]C=N[C:50]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O>FC(F)(F)C(O)=O.N[C@@H]1CC[C@H](CC#N)C1.CN(C=O)C>[C:50]([CH2:51][C@@H:52]1[CH2:53][CH2:6][C@H:5]([NH:4][C:30]([C:29]2[C:23]3[C:24](=[N:25][CH:26]=[C:21]([C:15]4[C:14]5[C:18](=[CH:19][C:11]([F:10])=[CH:12][CH:13]=5)[N:17]([CH3:20])[N:16]=4)[N:22]=3)[N:27]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:38])([CH3:39])[CH3:40])[CH:28]=2)=[O:32])[CH2:7]1)#[N:49]

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712796202-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 712855892-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-cyanomethyl-cyclopentyl)-amideYield 94%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 18453414(cis-3-Amino-cyclopentyl)-acetonitrile trifluoroacetateSolvent

Procedure

In a round-bottomed flask, (cis-3-amino-cyclopentyl)-acetonitrile trifluoroacetate (crude from Step 6) was dissolved in DMF (1.3 ml) and N,N-diisopropylethylamine (0.65 ml, 3.72 mmol) was added. Then, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (110 mg, 0.25 mmol) and HATU (104 mg, 0.27 mmol) were added. The yellow solution was stirred at room temperature for 48 h. Water and petroleum ether were added and the resulting suspension was filtered. The filter cake was washed with water and petroleum ether then dried under high vacuum to afford 128 mg (94%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-cyanomethyl-cyclopentyl)-amide as an off-white powder.

Workup

  1. filtrationthe resulting suspension was filtered
  2. washThe filter cake was washed with water and petroleum ether
  3. customthen dried under high vacuum

Sources & evidence

ORD record
ord-aca3186f0b79431b8442c235b246e711
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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