Ammonia → 6-Fluoro-3-((S)-1,4,4-trimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine

HRID 630842노트

반응식

HRID 630842 반응식
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:10]([C@@H:12]2[CH2:16][C:15]([CH3:18])([CH3:17])[CH2:14][N:13]2[CH3:19])=O)=[N:6][CH:7]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.ClC(Cl)(Cl)C(Cl)(Cl)Cl.N>C1COCC1.CO.C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:10]([C@@H:12]3[CH2:16][C:15]([CH3:18])([CH3:17])[CH2:14][N:13]3[CH3:19])=[N:9][N:8]=2)[CH:7]=1

참가 물질

9

반응물 5

HCID 222AmmoniaHCID 6214HexachloroethaneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86687127(S)-1,4,4-Trimethyl-pyrrolidine-2-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

생성물 1

HCID 866871286-Fluoro-3-((S)-1,4,4-trimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridine수율 84.6%

시약·촉매·용매 3

HCID 887Methanol용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of Intermediate 87b (950 mg, 3.57 mmol), Ph3P (1.87 g, 7.14 mmol) and Et3N (1.44 g, 14.28 mmol) in THF (40 mL) was added hexachloroethane (1.65 g, 7.14 mmol) and the mixture stirred at RT for 20 h. The reaction mixture was applied to an SCX-2 cartridge (70 g) and washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo gave a residue. FCC, using 0-10% [2M NH3 in MeOH] in DCM gave the title compound as a clear oil (750 mg, 84%). 1H NMR (400 MHz, CDCl3): 1.22 (3H, s), 1.24 (3H, s), 1.84 (1H, dd, J 12.7, 10.8), 2.04 (1H, dd, J 12.4, 7.4), 2.16 (3H, s), 2.25 (1H, d J, 9.1), 3.04 (1H, d, J 9.3), 4.22 (1H, dd, J 10.0, 7.6), 7.14-7.23 (1H, m), 7.69-7.77 (1H, m), 8.75-8.80 (1H, m).

후처리

  1. washwashed with MeOH
  2. washThe product was eluted with 2M NH3 in MeOH
  3. concentrationconcentration in vacuo
  4. customgave a residue

출처 및 근거

ORD 기록
ord-154d36b7b9ca4481bb5b8c9bd077e56b
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09315503B2

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