Triethylamine → tert-Butyl ((S)-1-(5-((S)-1-((2-amino-5-cyano-6-methylpyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)pyrrolidin-3-yl)(methyl)carbamate

HRID 2205598Notes

Reaction equation

HRID 2205598 reaction equation
[NH2:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]#[N:10])=[C:4]([CH3:11])[N:3]=1.[NH2:12][C@H:13]([C:15]1[N:20]=[C:19]2[CH:21]=[CH:22][N:23]([CH3:24])[C:18]2=[CH:17][C:16]=1[N:25]1[CH2:29][CH2:28][C@H:27]([N:30]([CH3:38])[C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:26]1)[CH3:14].C(N(CC)CC)C>CS(C)=O>[NH2:1][C:2]1[N:7]=[C:6]([NH:12][C@H:13]([C:15]2[N:20]=[C:19]3[CH:21]=[CH:22][N:23]([CH3:24])[C:18]3=[CH:17][C:16]=2[N:25]2[CH2:29][CH2:28][C@H:27]([N:30]([CH3:38])[C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:26]2)[CH3:14])[C:5]([C:9]#[N:10])=[C:4]([CH3:11])[N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 754124462-Amino-4-chloro-6-methyl-5-pyrimidinecarbonitrileHCID 118214738tert-Butyl ((S)-1-(5-((S)-1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)pyrrolidin-3-yl)(methyl)carbamate

Product 1

HCID 118214739tert-Butyl ((S)-1-(5-((S)-1-((2-amino-5-cyano-6-methylpyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)pyrrolidin-3-yl)(methyl)carbamateYield 68%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

To a 25 mL pear flask were added 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (63.4 mg, 0.376 mmol) and tert-butyl ((S)-1-(5-((S)-1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)pyrrolidin-3-yl)(methyl)carbamate (78 mg, 0.21 mmol) in DMSO (1.0 mL). Triethylamine (146 μL, 1.04 mmol) was added to the mixture, which was then heated to 90° C. for 2 hours. The reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over MgSO4, filtered, and concentrated. The residue was purified by liquid chromatography (SiO2, 25-100% EtOAc/heptanes gradient) to give the title compound as a foam (72 mg, 68%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.36-1.48 (m, 12H), 1.93-2.05 (m, 2H), 2.17-2.30 (m, 4H), 2.92 (s, 3H), 2.97-3.13 (m, 2H), 3.16-3.29 (m, 2H), 3.80 (s, 3H), 4.84 (br s, 1H), 5.71-5.89 (m, 1H), 6.39-6.55 (m, 1H), 6.84 (br s, 1H), 6.96 (d, J=7.58 Hz, 1H), 7.16 (br s, 1H), 7.55 (d, J=3.03 Hz, 1H), 7.85 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C26H35N9O2, 506. found 506.

Workup

  1. customThe reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by liquid chromatography (SiO2, 25-100% EtOAc/heptanes gradient)

Sources & evidence

ORD record
ord-1a9ae545398a48c0aceddfa4273bca79
Source dataset
uspto-grants-2016_06
Patent number
US09371321B2

Reaction notes

Loading…