N,N-Dimethylglycine → HCID 178461906, compound

HRID 243296Notes

Reaction equation

HRID 243296 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:16]([NH:18][C:19]2[N:27]=[CH:26][N:25]=[C:24]3[C:20]=2[N:21]=[CH:22][NH:23]3)[CH3:17])[CH2:3][CH2:2]1.[CH3:28][N:29]([CH2:31][C:32](O)=[O:33])[CH3:30].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[N:27]1[C:19]([NH:18][C@H:16]([C:8]2[N:7]([CH:4]3[CH2:5][CH2:6][N:1]([C:32](=[O:33])[CH2:31][N:29]([CH3:30])[CH3:28])[CH2:2][CH2:3]3)[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=2)[CH3:17])=[C:20]2[C:24]([NH:23][CH:22]=[N:21]2)=[N:25][CH:26]=1

Participants

6

Reactant 4

HCID 673N,N-DimethylglycineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178461903HCID 178461903, compound

Product 1

HCID 178461906HCID 178461906, compoundYield 33.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [(S)-1-(1-piperidin-4-yl-1H-benzoimidazol-2-yl)ethyl]-(9H-purin-6-yl)amine 113 (97 mg, 0.268 mmol), dimethylaminoacetic acid (30 mg, 0.294 mmol) and DIPEA (230 μL, 1.34 mmol) in DMF (5 mL) was added HATU (153 mg, 0.401 mmol) and the mixture was stirred at RT for 1 h. The crude reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined, then concentrated in vacuo, purified by column chromatography (Si—PCC, gradient 0-20% 2M NH3/MeOH in DCM) and triturated with diethyl ether. The product thus obtained was further purified by preparative HPLC (Phenomenex Gemini 5 μm C18 on a 20 min gradient 5-60% 0.1% NH4OH in acetonitrile/water) and loaded into an Isolute® SCX-2. The cartridge was washed with MeOH and the product eluted with 2M NH3/MeOH. The basic fractions were then combined and concentrated in vacuo affording 125 as a white solid (40 mg, 33%). LCMS: RT 1.67 min [M+H]+ 448.1. 1H NMR (CDCl3 plus MeOD, 400 MHz): δ 8.45 (1H, s), 7.94 (1H, s), 7.77 (1H, d, J=7.62 Hz), 7.41 (1H, d, J=7.73 Hz), 7.26-7.17 (3H, m), 6.10 (1H, s), 4.99-4.81 (1.5H, m), 4.64-4.53 (0.5H, m), 4.38-4.27 (0.5H, m), 4.21-4.08 (0.5H, m), 3.32-3.01 (2H, m), 2.87-2.16 (10H, m), 2.05-1.27 (6H, m). Signals split due to presence of rotamers

Workup

  1. customThe crude reaction mixture
  2. washwas washed with MeOH
  3. washthe product eluted with 2M NH3/MeOH
  4. additionThe product containing fractions
  5. concentrationconcentrated in vacuo
  6. custompurified by column chromatography (Si—PCC, gradient 0-20% 2M NH3/MeOH in DCM)
  7. customtriturated with diethyl ether
  8. customThe product thus obtained
  9. customwas further purified by preparative HPLC (Phenomenex Gemini 5 μm C18 on a 20 min gradient 5-60% 0.1% NH4OH in acetonitrile/water) and
  10. washThe cartridge was washed with MeOH
  11. washthe product eluted with 2M NH3/MeOH
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-be2f21dfa5194260ac23c50999ab899f
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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