Diisopropylethylamine → 2-(5-cyclopropyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

HRID 246198Notes

Reaction equation

HRID 246198 reaction equation
[CH:1]1([C:4]2[CH:5]=[C:6]3[C:10](=[CH:11][CH:12]=2)[N:9]([CH3:13])[N:8]=[C:7]3[C:14]2[N:15]=[C:16]3[C:22]([C:23](O)=[O:24])=[CH:21][N:20]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:17]3=[N:18][CH:19]=2)[CH2:3][CH2:2]1.Cl.[CH3:35][O:36][CH2:37][C@@H:38]([NH2:40])[CH3:39].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C(#N)C>[CH3:35][O:36][CH2:37][C@@H:38]([NH:40][C:23]([C:22]1[C:16]2[C:17](=[N:18][CH:19]=[C:14]([C:7]3[C:6]4[C:10](=[CH:11][CH:12]=[C:4]([CH:1]5[CH2:3][CH2:2]5)[CH:5]=4)[N:9]([CH3:13])[N:8]=3)[N:15]=2)[N:20]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:32])([CH3:33])[CH3:31])[CH:21]=1)=[O:24])[CH3:39]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 54596079(2S)-1-methoxypropan-2-amine hydrochlorideHCID 712800222-(5-cyclopropyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 712883672-(5-cyclopropyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amideYield 42.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 25 mL round-bottomed flask was charged with 2-(5-cyclopropyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (70 mg, 0.15 mmol), (S)-1-methoxypropan-2-amine hydrochloride (21 mg, 0.16 mmol), and HATU (63 mg, 0.16 mmol). Then added acetonitrile (2 mL) followed by N,N-diisopropylethylamine (0.08 mL, 0.45 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water. The mixture was extracted with ethyl acetate (3×). The organic layers were combined, dried over Na2SO4, and concentrated. The crude material was purified by flash chromatography over silica gel (gradient: 15% to 100% EtOAc in heptane) to afford 34 mg (42%) of 2-(5-cyclopropyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as a white solid.

Workup

  1. customthen quenched with water
  2. extractionThe mixture was extracted with ethyl acetate (3×)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude material was purified by flash chromatography over silica gel (gradient: 15% to 100% EtOAc in heptane)

Sources & evidence

ORD record
ord-77ac8a2141454991bedc9a31219eb8bc
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…