Diisopropylethylamine → (S)-tert-butyl 1-(4-(4-bromo-2-tert-butyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate

HRID 538408Notes

Reaction equation

HRID 538408 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:14]([CH3:17])([CH3:16])[CH3:15])[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9](Cl)[N:8]=1.[C:18]([O:22][C:23](=[O:29])[NH:24][C@@H:25]([CH3:28])[CH2:26][NH2:27])([CH3:21])([CH3:20])[CH3:19].C(N(C(C)C)CC)(C)C>C(#N)C.CCOC(C)=O>[Br:1][C:2]1[N:3]=[C:4]([C:14]([CH3:17])([CH3:16])[CH3:15])[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:27][CH2:26][C@@H:25]([NH:24][C:23](=[O:29])[O:22][C:18]([CH3:21])([CH3:20])[CH3:19])[CH3:28])[N:8]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 15030821tert-butyl N-[(2S)-1-aminopropan-2-yl]carbamate2×HCID 178441569HCID 178441569, compound

Product 1

HCID 178461767(S)-tert-butyl 1-(4-(4-bromo-2-tert-butyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamateYield 127.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 4-(4-bromo-2-tert-butyl-1H-imidazol-5-yl)-2-chloropyrimidine (2.0 g, 4.5 mmol; Example 6, Step 4), (S)-tert-butyl-1-aminopropan-2-ylcarbamate (1.0 g, 5.8 mmol; Example 23, Step 2), and diisopropylethyl amine (2.4 mL, 13.5 mmol) in dry acetonitrile was heated at 85° C. for 16 h. An additional charge of (S)-tert-butyl-1-aminopropan-2-ylcarbamate (145 mg, 0.8 mmol) was added and the reaction was maintained at 85° C. for 5 h. After allowing to cool to rt, the reaction was diluted with EtOAc (40 mL), washed with water (2×15 mL), dried (Na2SO4), and concentrated to provide 2.6 g of (S)-tert-butyl 1-(4-(4-bromo-2-tert-butyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate which was carried forward without further purification: LCMS (m/z): 585.0 (MH+), tR=1.07 min.

Workup

  1. additionwas added
  2. temperaturethe reaction was maintained at 85° C. for 5 h
  3. temperatureto cool to rt
  4. washwashed with water (2×15 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-3e16fe5418ca418cbf6905b1e00374c6
Source dataset
uspto-grants-2014_10
Patent number
US08865732B2

Reaction notes

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