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

HRID 1963930ノート

反応式

HRID 1963930 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-fbaa37a9cd964a2baae8633b7715f4f2
出典データセット
uspto-grants-2013_04
特許番号
US08415381B2

反応ノート

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