Diisopropylethylamine → (R)-Methyl 6-(2-(tert-butoxycarbonylamino)-3-ethoxypropylamino)-4-cyano-2-(m-tolylamino)nicotinate

HRID 2092810Notes

Reaction equation

HRID 2092810 reaction equation
Cl[C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:14][C:15]2[CH:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:31][CH2:32][C@@H:33]([NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[CH2:34][O:35][CH2:36][CH3:37]>CN(C=O)C.CCOC(C)=O>[C:41]([O:40][C:39]([NH:38][C@@H:33]([CH2:34][O:35][CH2:36][CH3:37])[CH2:32][NH:31][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:14][C:15]2[CH:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=2)[N:3]=1)=[O:45])([CH3:44])([CH3:43])[CH3:42]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 58317587Methyl 6-chloro-4-cyano-2-(m-tolylamino)nicotinateHCID 86654723tert-butyl N-((2R)-1-amino-3-ethoxypropan-2-yl)carbamate2×

Product 1

HCID 67238775(R)-Methyl 6-(2-(tert-butoxycarbonylamino)-3-ethoxypropylamino)-4-cyano-2-(m-tolylamino)nicotinate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 6-chloro-4-cyano-2-(m-tolylamino)nicotinate (200 mg, 0.663 mmol) in DMF (5 mL) was added DIPEA (0.232 mL, 1.326 mmol) and (R)-tert-butyl 1-amino-3-ethoxypropan-2-ylcarbamate (174 mg, 0.795 mmol). The reaction mixture was stirred at RT overnight. Additional (R)-tert-butyl 1-amino-3-ethoxypropan-2-ylcarbamate (231.25 mg, 1.061 mmol) was added and the mixture was heated at 65° C. for 1 h. After cooling to RT, the reaction mixture was diluted with EtOAc (30 mL) and washed with water (2×20 mL) and brine (20 mL). The combined organic layers were dried over Na2SO4 and concentrated to thick yellow oil. The crude product was used in the next step without further purification (415 mg). [M+H] calc'd for C25H33N5O5, 484. found, 484.

Workup

  1. temperaturethe mixture was heated at 65° C. for 1 h
  2. temperatureAfter cooling to RT
  3. washwashed with water (2×20 mL) and brine (20 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated to thick yellow oil
  6. customThe crude product was used in the next step without further purification (415 mg)

Sources & evidence

ORD record
ord-5da44e6648f04ee7b6b863a707357cad
Source dataset
uspto-grants-2013_05
Patent number
US08440689B2

Reaction notes

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