Triethylamine → N2'-((1R,3R)-3-aminocyclopentyl)-5'-chloro-N6-(3-fluorobenzyl)-2,4'-bipyridine-2',6-diamine

HRID 1963930Notes

Reaction equation

HRID 1963930 reaction equation
[Cl:1][C:2]1[C:3]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[N:16]=2)=[CH:4][C:5]([NH:8][C@@H:9]2[CH2:13][CH2:12][C@H:11](O)[CH2:10]2)=[N:6][CH:7]=1.ClC1C(C2C=CC=C(NCC3C=CC=C(F)C=3)N=2)=CC(F)=[N:35]C=1.N[C@@H]1CC[C@H](O)C1.C(N(CC)CC)C>CN1C(=O)CCC1>[NH2:35][C@@H:11]1[CH2:12][CH2:13][C@@H:9]([NH:8][C:5]2[CH:4]=[C:3]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=4)[N:16]=3)[C:2]([Cl:1])=[CH:7][N:6]=2)[CH2:10]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 20608641(1S,3R)-3-Aminocyclopentan-1-olHCID 58127193HCID 58127193, compoundHCID 66937090(1S,3R)-3-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)cyclopentanol

Product 1

HCID 58127237N2'-((1R,3R)-3-aminocyclopentyl)-5'-chloro-N6-(3-fluorobenzyl)-2,4'-bipyridine-2',6-diamine

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

Preparation of (1S,3R)-3-(5′-chloro-6-(3-fluorobenzylamino)-2,4′-bipyridin-2′-yl-amino)cyclopentanol: To 5′-chloro-2′-fluoro-N-(3-fluorobenzyl)-2,4′-bipyridin-6-amine (75 mg, 0.226 mmol), was added (1S,3R)-3-aminocyclopentanol (68.6 mg, 0.678 mmol), NMP (0.75 ml) and triethylamine (0.158 ml, 1.130 mmol). The crude reaction mixture was stirred at 100° C. for 18 hr, and the reaction progress followed by LCMS. The crude reaction mixture was cooled, filtered, and purified by prep LC. The product fractions were collected, 50 mL of 1 M NaOH and 50 mL of EtOAc were added. The aqueous layer was removed, the organic layer was washed with 50 mL of saturated salt solution, dried over sodium sulfate, and reduced to constant mass. 28 mg of the desired compound was obtained. LCMS (m/z): 413.1 (MH+), retention time=0.67 min.; 1H NMR (400 MHz, CHLOROFORM-d, 25° C.) δ ppm 1.71 (d, J=14.09 Hz, 1 H) 1.75-1.91 (m, 2 H) 1.97-2.05 (m, 1 H) 2.10-2.16 (m, 1 H) 2.61 (br. s., 1 H) 4.03-4.18 (m, 1 H) 4.39 (tt, J= 4.84, 2.59 Hz, 1 H) 4.55 (d, J= 5.09 Hz, 2 H) 5.19 (br. s., 2 H) 6.41 (d, J= 8.22 Hz, 1 H) 6.55 (s, 1 H) 6.90-7.02 (m, 2 H) 7.05-7.18 (m, 2 H) 7.24-7.34 (m, 1 H) 7.43-7.55 (m, 1 H) 8.07 (s, 1 H).

Workup

  1. customThe crude reaction mixture
  2. customThe crude reaction mixture
  3. temperaturewas cooled
  4. filtrationfiltered
  5. custompurified by prep LC
  6. customThe product fractions were collected
  7. addition50 mL of 1 M NaOH and 50 mL of EtOAc were added
  8. customThe aqueous layer was removed
  9. washthe organic layer was washed with 50 mL of saturated salt solution
  10. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-fbaa37a9cd964a2baae8633b7715f4f2
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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