Diisopropylethylamine → Methyl 6-(cis-4-Aminotetrahydrofuran-3-ylamino)-4-cyano-2-(m-tolylamino)nicotinate

HRID 516051Notes

Reaction equation

HRID 516051 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.[O:31]1[CH2:35][C@@H:34]([NH2:36])[C@@H:33]([NH2:37])[CH2:32]1>CN(C=O)C.CO>[NH2:36][C@H:34]1[CH2:35][O:31][CH2:32][C@H:33]1[NH:37][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

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 14171649cis-3,4-TetrahydrofurandiamineHCID 58317587Methyl 6-chloro-4-cyano-2-(m-tolylamino)nicotinate

Product 1

HCID 67239207Methyl 6-(cis-4-Aminotetrahydrofuran-3-ylamino)-4-cyano-2-(m-tolylamino)nicotinateYield 73%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 6-chloro-4-cyano-2-(m-tolylamino)nicotinate (40 mg, 0.133 mmol) in DMF (1 mL) was added DIPEA (0.046 mL, 0.265 mmol) and (3R,4S)-tetrahydrofuran-3,4-diamine (13.54 mg, 0.133 mmol). The mixture was stirred at RT overnight. Additional amine was added and the reaction mixture was stirred at RT for an additional day. The reaction mixture was diluted in MeOH (10 mL) and purified by reverse phase preparative HPLC. The 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 (35.5 mg, 73%). [M+H] calc'd for C19H21N5O3, 368; found, 368.

Workup

  1. stirringthe reaction mixture was stirred at RT for an additional day
  2. custompurified by reverse phase preparative HPLC
  3. customThe fractions were collected
  4. customACN was removed via rotary evaporation
  5. washwashed with EtOAc (2×200 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customThe organic phase was stripped to dryness via rotary evaporation

Sources & evidence

ORD record
ord-98d45ec6e3d741a99589761bb88cdd39
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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