Dimethyl Sulfoxide → 2-((1S)-1-((6-amino-5-(methylsulfonyl)-4-pyrimidinyl)amino)ethyl)-1-cyclopropyl-N-methyl-1H-benzimidazole-7-carboxamide

HRID 2036585Notes

Reaction equation

HRID 2036585 reaction equation
[CH3:1][S:2]([O-:4])=[O:3].[Na+].[NH2:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]([NH:13][C@H:14]([C:16]2[N:20]([CH:21]3[CH2:23][CH2:22]3)[C:19]3[C:24]([C:28]([NH:30][CH3:31])=[O:29])=[CH:25][CH:26]=[CH:27][C:18]=3[N:17]=2)[CH3:15])[C:8]=1I.CNCCNC.CS(C)=O>CCOC(C)=O.[O-]S(C(F)(F)F)(=O)=O.[Cu+2].[O-]S(C(F)(F)F)(=O)=O>[NH2:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]([NH:13][C@H:14]([C:16]2[N:20]([CH:21]3[CH2:23][CH2:22]3)[C:19]3[C:24]([C:28]([NH:30][CH3:31])=[O:29])=[CH:25][CH:26]=[CH:27][C:18]=3[N:17]=2)[CH3:15])[C:8]=1[S:2]([CH3:1])(=[O:4])=[O:3]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8070N,N'-DimethylethylenediamineHCID 2733271Sodium methanesulfinateHCID 58459347(S)-2-(1-(6-amino-5-iodopyrimidin-4-ylamino)ethyl)-1-cyclopropyl-N-methyl-1H-benzo[d]imidazole-7-carboxamide

Product 1

HCID 534828162-((1S)-1-((6-amino-5-(methylsulfonyl)-4-pyrimidinyl)amino)ethyl)-1-cyclopropyl-N-methyl-1H-benzimidazole-7-carboxamide

Reagents, catalysts & solvents 2

HCID 2734996copper(II) trifluoromethanesulfonateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of copper(II) triflate (7.6 mg, 0.021 mmol), sodium methanesulfinate (25.7 mg, 0.251 mmol), (S)-2-(1-(6-amino-5-iodopyrimidin-4-ylamino)ethyl)-1-cyclopropyl-N-methyl-1H-benzo[d]imidazole-7-carboxamide (prepared in Example 21, 100 mg, 0.210 mmol) under N2, N,N′-dimethylethylenediamine (4.52 μL, 0.042 mmol) and DMSO (1 mL) were added. The mixture was placed in a 110° C. oil bath. After stirring for 18 h at 110° C., the mixture was cooled to rt, diluted with EtOAc, and filtered through a pad of silica gel. The filtrate was washed with water, brine, dried and concentrated under reduced pressure. The residue was purified by column chromatography on a silica gel column using 0 to 10% gradient of MeOH in DCM-EtOAc (1:1) 0.2% NH4OH as eluent to give 2-((1S)-1-((6-amino-5-(methylsulfonyl)-4-pyrimidinyl)amino)ethyl)-1-cyclopropyl-N-methyl-1H-benzimidazole-7-carboxamide: 1H NMR (400 MHz, CDCl3) 8.02-7.97 (m, 2H), 7.65 (d, J=8 Hz, 1H), 7.22 (d, J=8 Hz, 1H), 7.12 (dd, J=8, 8 Hz, 1H), 6.01-5.92 (m, 2H), 3.45-3.40 (m, 2H), 3.16 (s, 3H), 3.01 (d, J=4 Hz, 3H), 1.61 (d, J=4 Hz, 3H), 1.22-1.10 (m, 2H), 1.04-0.96 (m, 1H), 0.80-0.73 (m, 1H); LC-MS (ESI) m/z 430.1 [M+H]+.

Workup

  1. customwas placed in a 110° C.
  2. temperaturethe mixture was cooled to rt
  3. filtrationfiltered through a pad of silica gel
  4. washThe filtrate was washed with water, brine
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on a silica gel column

Sources & evidence

ORD record
ord-8f2f73efdf354652b9accc64a742c95e
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

Loading…