Sodium hydride → tert-butyl 2-cyclohexyl-2-oxoethyl(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)carbamate

HRID 1854387Notes

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]([CH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1)=[O:33]>CN(C=O)C>[CH:34]1([C:32](=[O:33])[CH2:31][N:22]([C:20]2[N:21]=[C:16]3[CH:15]=[CH:14][N:13]([S:3]([C:6]4[CH:7]=[CH:8][C:9]([CH3:10])=[CH:11][CH:12]=4)(=[O:5])=[O:4])[C:17]3=[N:18][CH:19]=2)[C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:28])[CH3:27])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1

Participants

Conditions

Temperature: 0 °C

Procedure

NaH (60% in mineral oil, 0.020 g, 0.49 mmol) was added to dry DMF (3 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 (0.19 g, 0.489 mmol, Example #8, Step A) in dry DMF (2 mL) was added drop-wise. The reaction mixture was allowed to warm to ambient temperature and 2-bromo-1-cyclohexylethanone (0.10 g, 0.49 mmol, 3B PharmaChem) was added. The reaction mixture was stirred for about 2 h and then concentrated under reduced pressure. Purification by silica gel flash chromatography eluting with 100% heptane for 10 min and a gradient of 10-20% EtOAc in heptane over 20 min yielded tert-butyl 2-cyclohexyl-2-oxoethyl(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)carbamate as a yellow amorphous solid (0.080 g, 32%): LC/MS (Table 2, Method a) Rt=3.13 min; MS m/z: 513 (M+H)+.

Workup

temperatureto warm to ambient temperature
concentrationconcentrated under reduced pressure
customPurification by silica gel flash chromatography
washeluting with 100% heptane for 10 min

Sources & evidence

ORD record: ord-4d644cc8396442ce889710cabc616326
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962629B2

Reaction notes

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