Diisopropylethylamine → (S)-4-Amino-6-((1-(1-methyl-6-(thiazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-2-(methylthio)pyrimidine-5-carbonitrile

HRID 75297Notes

Reaction equation

HRID 75297 reaction equation
Cl.Cl.[CH3:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([C@@H:18]([NH2:20])[CH3:19])=[C:10]([C:13]3[N:14]=[CH:15][S:16][CH:17]=3)[CH:11]=2)[CH:6]=[CH:5]1.[NH2:21][C:22]1[C:27]([C:28]#[N:29])=[C:26](Cl)[N:25]=[C:24]([S:31][CH3:32])[N:23]=1.C(N(C(C)C)C(C)C)C>C(#N)C>[NH2:21][C:22]1[C:27]([C:28]#[N:29])=[C:26]([NH:20][C@H:18]([C:9]2[N:8]=[C:7]3[CH:6]=[CH:5][N:4]([CH3:3])[C:12]3=[CH:11][C:10]=2[C:13]2[N:14]=[CH:15][S:16][CH:17]=2)[CH3:19])[N:25]=[C:24]([S:31][CH3:32])[N:23]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 40931594-Amino-6-chloro-2-(methylthio)-5-pyrimidinecarbonitrileHCID 86707989(S)-1-(1-methyl-6-(thiazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine dihydrochloride

Product 1

HCID 86707988(S)-4-Amino-6-((1-(1-methyl-6-(thiazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-2-(methylthio)pyrimidine-5-carbonitrileYield 9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

(S)-1-(1-methyl-6-(thiazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine dihydrochloride (200 mg, 0.604 mmol), 4-amino-6-chloro-2-(methylthio)pyrimidine-5-carbonitrile (182 mg, 0.906 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.315 mL, 1.81 mmol) were combined in acetonitrile (6 mL). The reaction mixture was heated in a microwave reactor at 120° C. for 2 hours and then concentrated. The residue was dissolved in MeOH/DCM, absorbed onto silica gel, and purified by column chromatography eluting with 20-80% EtOAc in hexane over 60 minutes. The fractions containing the desired product were collected and concentrated to give the title compound (22 mg, 9%). ESI-MS m/z [M+H]+ calc'd for C19H18N8S2, 423; found 423.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in MeOH/DCM
  3. customabsorbed onto silica gel
  4. custompurified by column chromatography
  5. washeluting with 20-80% EtOAc in hexane over 60 minutes
  6. additionThe fractions containing the desired product
  7. customwere collected
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-da0d7a9971ce46baa1311ee118530eec
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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