Diisopropylethylamine → (R)-Methyl 6-(2-(tert-butoxycarbonylamino)-3-methoxypropylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate

HRID 711550Notes

Reaction equation

HRID 711550 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]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)[N:3]=1.[NH2:20][CH2:21][C@@H:22]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:23][O:24][CH3:25].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[C:29]([O:28][C:27]([NH:26][C@@H:22]([CH2:23][O:24][CH3:25])[CH2:21][NH:20][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)[N:3]=1)=[O:33])([CH3:32])([CH3:31])[CH3:30]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 58317582methyl 6-chloro-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinateHCID 59199768tert-butyl N-((2R)-1-amino-3-methoxypropan-2-yl)carbamate

Product 1

HCID 67238066(R)-Methyl 6-(2-(tert-butoxycarbonylamino)-3-methoxypropylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

To a screw-top vial was added methyl 6-chloro-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate (115 mg, 0.416 mmol), (R)-tert-butyl 1-amino-3-methoxypropan-2-ylcarbamate (93 mg, 0.457 mmol), and DIPEA (87 μL, 0.499 mmol) in DMF (308 μL). The resulting yellow solution was stirred for 12 h at 45° C. and then at 50° C. for 6 h. The reaction mixture was diluted with EtOAc (20 mL) and was washed with water (10 mL) and brine (20 mL). The organic layer was collected and dried over Na2SO4 and was concentrated to a yellow oil. The concentrate was purified via standard phase column chromatography eluting with EtOAc and hexanes (50-100% EtOAc gradient) to give the title compound as a light yellow residue (36.5 mg, 20%). [M+H] calc'd for C21H28N6O5, 445. found, 445.

Workup

  1. waitat 50° C. for 6 h
  2. washwas washed with water (10 mL) and brine (20 mL)
  3. customThe organic layer was collected
  4. dry with materialdried over Na2SO4
  5. concentrationwas concentrated to a yellow oil
  6. customThe concentrate was purified via standard phase column chromatography
  7. washeluting with EtOAc and hexanes (50-100% EtOAc gradient)

Sources & evidence

ORD record
ord-41c3b0a1b8834706b38a99b096ab0703
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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