Triethylamine → 2,4-Diamino-6-((1-(6-(4-hydroxy-4-methylpiperidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrile

HRID 75326Notes

Reaction equation

HRID 75326 reaction equation
[NH2:1][CH:2]([C:4]1[N:9]=[C:8]2[CH:10]=[CH:11][N:12]([CH3:13])[C:7]2=[CH:6][C:5]=1[N:14]1[CH2:19][CH2:18][C:17]([CH3:21])([OH:20])[CH2:16][CH2:15]1)[CH3:3].[NH2:22][C:23]1[N:28]=[C:27]([NH2:29])[C:26]([C:30]#[N:31])=[C:25](Cl)[N:24]=1.CCN(CC)CC>CN(C=O)C>[NH2:22][C:23]1[N:28]=[C:27]([NH2:29])[C:26]([C:30]#[N:31])=[C:25]([NH:1][CH:2]([C:4]2[N:9]=[C:8]3[CH:10]=[CH:11][N:12]([CH3:13])[C:7]3=[CH:6][C:5]=2[N:14]2[CH2:15][CH2:16][C:17]([OH:20])([CH3:21])[CH2:18][CH2:19]2)[CH3:3])[N:24]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 867080001-(5-(1-Aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-4-methylpiperidin-4-olHCID 867080212,4-Diamino-6-chloropyrimidine-5-carbonitrile

Product 1

HCID 730548282,4-Diamino-6-((1-(6-(4-hydroxy-4-methylpiperidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrileYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a 10 mL vial were added 1-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-4-methylpiperidin-4-ol (56 mg, 0.194 mmol), 2,4-diamino-6-chloropyrimidine-5-carbonitrile (32.9 mg, 0.194 mmol) and Et3N (0.054 mL, 0.388 mmol) in DMF (3 mL). The resulting yellow solution was heated to 90° C. and stirred overnight. The reaction mixture was purified by preparative HPLC eluting with 5-30% ACN in water (with 0.05% ammonium carbonate). The fractions containing the desired product were combined and lyophilized to give the title compound (racemate) as a white solid (40 mg, 49%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.17-1.29 (m, 3 H), 1.32-1.43 (m, 3 H), 1.52-1.87 (m, 4 H), 2.57-2.72 (m, 2 H), 2.73-2.94 (m, 2 H), 3.16-3.29 (m, 1 H), 3.71-3.86 (m, 3 H), 4.24-4.32 (m, 1 H), 5.74-5.88 (m, 1 H), 6.34-6.44 (m, 2 H), 6.44-6.52 (m, 1 H), 6.53-6.65 (m, 3 H), 7.48-7.58 (m, 1 H), 7.77-7.84 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C21H27N9O, 422.2; found 422.5.

Workup

  1. customThe reaction mixture was purified by preparative HPLC
  2. washeluting with 5-30% ACN in water (with 0.05% ammonium carbonate)
  3. additionThe fractions containing the desired product

Sources & evidence

ORD record
ord-ddf8907f2c834be08b6e0f191350fc55
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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