Water → 2-[1-(1-tert-butoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246286Notes

Reaction equation

HRID 246286 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([F:23])[CH:21]=3)[C:16]([C:24]3[N:25]=[C:26]4[C:32]([C:33](O)=[O:34])=[CH:31][N:30]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:27]4=[N:28][CH:29]=3)=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:44]([NH2:48])([CH3:47])([CH3:46])[CH3:45].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O>CN(C=O)C>[C:44]([NH:48][C:33]([C:32]1[C:26]2[C:27](=[N:28][CH:29]=[C:24]([C:16]3[C:17]4[C:22](=[CH:21][C:20]([F:23])=[CH:19][CH:18]=4)[N:14]([CH:11]4[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]4)[N:15]=3)[N:25]=2)[N:30]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[CH:31]=1)=[O:34])([CH3:47])([CH3:46])[CH3:45]

Participants

6

Reactant 4

HCID 962WaterHCID 6385Tert-ButylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712802552-[1-(1-tert-butoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 712800342-[1-(1-tert-butoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 10 ml round-bottomed flask, 2-[1-(1-tert-butoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (85 mg, 0.14 mmol) was dissolved in DMF (1.5 ml) and tert-butylamine (0.06 ml, 0.57 mmol) and HATU (59 mg, 0.155 mmol) were added. The light yellow suspension was stirred at room temperature overnight then water and petroleum ether were added. The resulting suspension was filtered. The filter cake was washed with water and petroleum ether then dried under high vacuum. The residue was chromatographed over 8 g silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc) to afford 47 mg (51%) of 2-[1-(1-tert-butoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as an off-white solid.

Workup

  1. filtrationThe resulting suspension was filtered
  2. washThe filter cake was washed with water and petroleum ether
  3. customthen dried under high vacuum
  4. customThe residue was chromatographed over 8 g silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc)

Sources & evidence

ORD record
ord-5051a10f5af44951806232aa6c3bc959
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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