Methylamine → HCID 21104328, compound

HRID 1010871Notes

Reaction equation

HRID 1010871 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([C:8]2[N:13]=[C:12]([NH:14][C:15]3[C:20]([C:21](O)=[O:22])=[CH:19][N:18]=[CH:17][CH:16]=3)[C:11]3[CH:24]([CH3:27])[CH2:25][CH2:26][C:10]=3[N:9]=2)[CH:7]=1.[CH2:29]([N:31](CC)CC)C.CN.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([C:8]2[N:13]=[C:12]([NH:14][C:15]3[C:20]([C:21]([NH:31][CH3:29])=[O:22])=[CH:19][N:18]=[CH:17][CH:16]=3)[C:11]3[CH:24]([CH3:27])[CH2:25][CH2:26][C:10]=3[N:9]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 2724699PyBOPHCID 21104327HCID 21104327, compound

Product 1

HCID 21104328HCID 21104328, compoundYield 58.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of 4-[2-(5-chloro-2-fluorophenyl)-5-methyl-6,7-dihydro-5H-cyclopentapyrimidin-4-ylamino]-nicotinic acid (20 mg, 0.05 mmol, 1 eq) in DMF (2 ml) was added triethylamine (8 μl, 0.05 mmol, 1.1 eq) followed by methylamine (250 μl, 3.89 mmol, 2 M solution in THF, 10 eq). To the suspension was added a solution of PyBOP (40 mg, 0.08 mmol, 1.5 eq) in DMF (1 ml) dropwise. The reaction mixture was stirred at room temperature for 16 h. The reaction was concentrated in vacuo and the residue was triturated with ether (2×20 ml). The crude residue was purified by flash column chromatography (100% ethylacetate) to afford 4-[2-(5-chloro-2-fluorophenyl)-5-methyl-6,7-dihydro-5H-cyclopentapyrimidin-4-ylamino]-N-methyl-nicotinamide, i.e. compound of formula (47), (12 mg, 58%) as a white solid. Compound of formula (46) was prepared by the method described for the synthesis of compound of formula (47) employing ammonia in place of methylamine.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customthe residue was triturated with ether (2×20 ml)
  3. customThe crude residue was purified by flash column chromatography (100% ethylacetate)

Sources & evidence

ORD record
ord-e679ca8cda3e4d81a69abaea23fdbe51
Source dataset
uspto-grants-2011_07
Patent number
US07977342B2

Reaction notes

Loading…