Sodium hydride → HCID 58010029, compound

HRID 2204582Notes

Reaction equation

HRID 2204582 reaction equation
[H-].[Na+].[S:3]([N:13]1[C:17]2=[N:18][CH:19]=[C:20]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[N:21]=[C:16]2[CH:15]=[CH:14]1)([C:6]1[CH:12]=[CH:11][C:9]([CH3:10])=[CH:8][CH:7]=1)(=[O:5])=[O:4].Br[CH2:31][C:32]([C@@H:34]1[CH2:39][CH2:38][CH2:37][N:36]([C:40]([O:42][CH2:43][CH:44]2[C:56]3[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=3[C:50]3[C:45]2=[CH:46][CH:47]=[CH:48][CH:49]=3)=[O:41])[CH2:35]1)=[O:33]>CN(C=O)C>[CH:46]1[C:45]2[CH:44]([CH2:43][O:42][C:40]([N:36]3[CH2:37][CH2:38][CH2:39][C@@H:34]([C:32](=[O:33])[CH2:31][N:22]([C:23]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:29])[C:20]4[N:21]=[C:16]5[CH:15]=[CH:14][N:13]([S:3]([C:6]6[CH:7]=[CH:8][C:9]([CH3:10])=[CH:11][CH:12]=6)(=[O:5])=[O:4])[C:17]5=[N:18][CH:19]=4)[CH2:35]3)=[O:41])[C:56]3[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=3)[C:50]=2[CH:49]=[CH:48][CH:47]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 580097831,1-Dimethylethyl N-(5-((4-methylphenyl)sulfonyl)-5H-pyrrolo(2,3-b)pyrazin-2-yl)carbamateHCID 58010084HCID 58010084, compound

Product 1

HCID 58010029HCID 58010029, compoundYield 28.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

NaH (60% dispersion in mineral oil, 0.041 g, 1.0 mmol) was added to anhydrous DMF (5 mL). The suspension was cooled to about 0° C. and a solution of tert-butyl 5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-ylcarbamate (0.40 g, 1.0 mmol) in anhydrous DMF (5 mL) was added drop-wise. The reaction mixture was allowed to warm to ambient temperature and (R)-(9H-fluoren-9-yl)methyl 3-(2-bromoacetyl)piperidine-1-carboxylate (0.441 g, 1.03 mmol, Preparation #LL.1) was added. The reaction mixture was stirred for about 30 min before it was partitioned between EtOAc (30 mL) and brine (2×100 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (12 g column) eluting with a gradient of 10-50% EtOAc in heptane to give (R)-(9H-fluoren-9-yl)methyl-3-(2-(tert-butoxycarbonyl(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)amino)acetyl)piperidine-1-carboxylate as a clear oil (0.21 g, 26%): LC/MS (Table 2, Method a) Rt=3.16 min; MS m/z: 736 (M+H)+.

Workup

  1. temperatureto warm to ambient temperature
  2. customwas partitioned between EtOAc (30 mL) and brine (2×100 mL)
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (12 g column)
  7. washeluting with a gradient of 10-50% EtOAc in heptane

Sources & evidence

ORD record
ord-f9d430fd70404699b253323a81ecc717
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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