Diisopropylethylamine → Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(1-ethyl-1H-pyrazol-4-yl)nicotinate

HRID 711516Notes

Reaction equation

HRID 711516 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]([CH2:19][CH3:20])[CH:18]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:30][C@@H:31]1[CH2:36][CH2:35][CH2:34][CH2:33][C@@H:32]1[NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41]>CN(C=O)C>[C:40]([O:39][C:38]([NH:37][C@H:32]1[CH2:33][CH2:34][CH2:35][CH2:36][C@H:31]1[NH:30][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]([CH2:19][CH3:20])[CH:18]=2)[N:3]=1)=[O:44])([CH3:43])([CH3:41])[CH3:42]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 58317713Methyl 6-chloro-4-cyano-2-(1-ethyl-1H-pyrazol-4-yl)nicotinate

Product 1

HCID 67237978Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(1-ethyl-1H-pyrazol-4-yl)nicotinateYield 19.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 6-chloro-4-cyano-2-(1-ethyl-1H-pyrazol-4-yl)nicotinate (201 mg, 0.691 mmol) in DMF (1 mL) was added DIPEA (0.242 mL, 1.383 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (237 mg, 1.106 mmol). The reaction mixture was stirred at 100° C. overnight, after which the solvent was removed, and the resulting crude material was diluted in MeOH (5.0 mL) and purified via reverse phase preparative HPLC. The collected fractions were collected and ACN was removed via rotary evaporation. The resulting aq solution was neutralized with saturated aq NaHCO3 and washed with EtOAc (2×200 mL), dried over Na2SO4, and filtered. The organic phase was stripped to dryness via rotary evaporation to yield the title compound (62 mg, 19%). [M+H] calc'd for C24H32N6O4, 469. found, 469.

Workup

  1. customafter which the solvent was removed
  2. additionthe resulting crude material was diluted in MeOH (5.0 mL)
  3. custompurified via reverse phase preparative HPLC
  4. customThe collected fractions were collected
  5. customACN was removed via rotary evaporation
  6. washwashed with EtOAc (2×200 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customThe organic phase was stripped to dryness via rotary evaporation

Sources & evidence

ORD record
ord-0f443cd17a214e1691f28dc7b8aa4a95
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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