Diisopropylethylamine → HCID 58084368, compound

HRID 2174650Notes

Reaction equation

HRID 2174650 reaction equation
[NH:1]1[CH2:5][CH2:4][CH:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:2]1.Br[C:15]1[C:16]([NH2:33])=[N:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([S:27]([CH:30]([CH3:32])[CH3:31])(=[O:29])=[O:28])=[CH:23][CH:22]=2)[N:20]=1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[NH2:33][C:16]1[C:15]([N:1]2[CH2:5][CH2:4][CH:3]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:12])[CH3:11])[CH2:2]2)=[N:20][C:19]([C:21]2[CH:22]=[CH:23][C:24]([S:27]([CH:30]([CH3:32])[CH3:31])(=[O:29])=[O:28])=[CH:25][CH:26]=2)=[CH:18][N:17]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 580843723-Bromo-5-(4-(isopropylsulfonyl)phenyl)pyrazin-2-amine

Product 1

HCID 58084368HCID 58084368, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl N-pyrrolidin-3-ylcarbamate (43.14 mg, 0.2316 mmol) was added to a stirred solution of 3-bromo-5-(4-(isopropylsulfonyl)phenyl)pyrazin-2-amine (75 mg, 0.2105 mmol) and DIPEA (29.93 mg, 40.34 μL, 0.2316 mmol) in NMP (1 mL) and the reaction mixture heated to 100° C. under microwave conditions for 90 minutes. The reaction mixture was partitioned between EtOAc/water and the layers separated. The aqueous layer was extracted with EtOAc (×3) and the combined organic extracts washed with brine (×2), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 12 g column, eluting with 0 to 100% EtOAc/Petroleum Ether). The fractions were collected concentrated in vacuo and freeze-dried to give the title compound as a yellow solid (46 mg, 48% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.17 (d, 6H), 1.40 (s, 9H), 1.79-1.82 (m, 1H), 2.08-2.17 (m, 1H), 3.30-3.38 (m, 1H), 3.42-3.44 (m, 2H), 3.60-3.71 (m, 2H), 4.06-4.12 (m, 1H), 6.22 (s, 2H), 7.16 (d, 1H), 7.83 (d, 2H), 8.18 (d, 2H) and 8.20 (s, 1H) ppm; (ES+) 462.3.

Workup

  1. customThe reaction mixture was partitioned between EtOAc/water
  2. customthe layers separated
  3. extractionThe aqueous layer was extracted with EtOAc (×3)
  4. washthe combined organic extracts washed with brine (×2)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (ISCO Companion™, 12 g column, eluting with 0 to 100% EtOAc/Petroleum Ether)
  9. customThe fractions were collected
  10. concentrationconcentrated in vacuo
  11. customfreeze-dried

Sources & evidence

ORD record
ord-c944c52a6484442ab74a32b39fce39d2
Source dataset
uspto-grants-2015_06
Patent number
US09062008B2

Reaction notes

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