Trifluoroacetic acid → Trifluoroacetic acid

HRID 2205627Notes

Reaction equation

HRID 2205627 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:16]=[C:15]3[CH:17]=[CH:18][N:19]([CH3:20])[C:14]3=[CH:13][C:12]=2[N:21]([CH3:33])[CH:22]2[CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23]2)[CH3:10])[C:5]([C:34]#[N:35])=[C:4]([CH3:36])[N:3]=1.[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38]>ClCCl>[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38].[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:16]=[C:15]3[CH:17]=[CH:18][N:19]([CH3:20])[C:14]3=[CH:13][C:12]=2[N:21]([CH:22]2[CH2:23][NH:24][CH2:25]2)[CH3:33])[CH3:10])[C:5]([C:34]#[N:35])=[C:4]([CH3:36])[N:3]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118214762tert-Butyl (S)-3-((5-(1-((2-amino-5-cyano-6-methylpyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)(methyl)amino)azetidine-1-carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 118207721(S)-2-Amino-4-((1-(6-(azetidin-3-yl(methyl)amino)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-6-methylpyrimidine-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Crude tert-butyl (S)-3-((5-(1-((2-amino-5-cyano-6-methylpyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)(methyl)amino)azetidine-1-carboxylate was dissolved in dichloromethane (1 mL). To this solution was added TFA (0.462 mL, 6.00 mmol) at room temperature. The reaction mixture was stirred at room temperature for 5 minutes. The solvent was removed with a stream of nitrogen and the crude product was purified by preparative HPLC (acid mode, 1-25% ACN/water gradient) to give a TFA salt of the title compound as a clear film (5.9 mg, 19% over two steps). 1H NMR (400 MHz, CD3OD) δ ppm 1.73-1.82 (m, 3H), 2.49-2.56 (m, 3H), 2.82-2.89 (m, 3H), 3.94-4.08 (m, 4H), 4.19-4.33 (m, 3H), 4.46-4.57 (m, 1H), 5.97-6.09 (m, 1H), 6.70-6.77 (m, 1H), 7.85-7.94 (m, 1H), 8.32-8.47 (m, 1H). ESI-MS m/z [M+H]+ calc'd for C20H25N9, 392. found 392.

Workup

  1. customThe solvent was removed with a stream of nitrogen
  2. customthe crude product was purified by preparative HPLC (acid mode, 1-25% ACN/water gradient)

Sources & evidence

ORD record
ord-5f8222edac7c4264ae71a5bee923c2dd
Source dataset
uspto-grants-2016_06
Patent number
US09371321B2

Reaction notes

Loading…