Triethylamine → HCID 118230347, compound

HRID 2205614Notes

Reaction equation

HRID 2205614 reaction equation
[NH2:1][C@H: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][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)[CH3:3].[NH2:27][C:28]1[N:33]=[C:32]([NH2:34])[C:31]([C:35]#[N:36])=[C:30](Cl)[N:29]=1.C(N(CC)CC)C>CS(C)=O>[NH2:27][C:28]1[N:29]=[C:30]([NH:1][C@H: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][N:17]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:18][CH2:19]2)[CH3:3])[C:31]([C:35]#[N:36])=[C:32]([NH2:34])[N:33]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 867080212,4-Diamino-6-chloropyrimidine-5-carbonitrileHCID 118207781HCID 118207781, compound

Product 1

HCID 118230347HCID 118230347, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
95 °C

Procedure

To a 25 mL pear flask were added tert-butyl (S)-4-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)piperazine-1-carboxylate (0.076 g, 0.21 mmol) and 2,4-diamino-6-chloropyrimidine-5-carbonitrile (0.054 g, 0.32 mmol) in DMSO (1 mL) to give a yellow suspension. Triethylamine (0.088 mL, 0.63 mmol) was added and the mixture was heated to 95° C. for 2 hours. The reaction appeared to stall so 1 equivalent of triethylamine was added. After a total of 4 hours of heating, the mixture was cooled and 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 crude product was purified by preparative HPLC (acid mode, 20-25% ACN/water gradient). The product-containing fractions were combined, neutralized with a small amount of saturated NaHCO3, concentrated in vacuo to remove ACN, and then extracted with EtOAc. The organic layers were combined, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound as a pale beige solid (37 mg, 36%). 1H NMR (400 MHz, CDCl3) δ ppm 1.43 (s, 11H), 1.87 (br s, 2H), 2.72 (br s, 2H), 2.97 (br s, 2H), 3.70 (s, 3H), 4.80-5.11 (m, 4H), 5.92 (br s, 1H), 6.59 (d, J=2.27 Hz, 1H), 6.76 (d, J=6.06 Hz, 1H), 7.16 (d, J=2.78 Hz, 2H), 7.32 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C24H32N10O2, 493. found 493.

Workup

  1. customto give a yellow suspension
  2. additionwas added
  3. temperatureAfter a total of 4 hours of heating
  4. temperaturethe mixture was cooled
  5. customthe reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by preparative HPLC (acid mode, 20-25% ACN/water gradient)
  11. concentrationconcentrated in vacuo
  12. customto remove ACN
  13. extractionextracted with EtOAc
  14. dry with materialdried over MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-38d991d58ea4486eae843822c515ecd7
Source dataset
uspto-grants-2016_06
Patent number
US09371321B2

Reaction notes

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