Triethylamine → (S)-4-Chloro-2-fluorobenzyl-[1-(6-fluoropyridin-3-yl)-pyrrolidin-3-yl]-amine

HRID 252112

반응식

HRID 252112 반응식
Cl.[F:2][C:3]1[N:8]=[CH:7][C:6]([N:9]2[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[C:25]([F:31])[CH:24]=1.[BH4-].[Na+]>CO>[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][NH:14][C@H:11]2[CH2:12][CH2:13][N:9]([C:6]3[CH:7]=[N:8][C:3]([F:2])=[CH:4][CH:5]=3)[CH2:10]2)=[C:25]([F:31])[CH:24]=1

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 27249084-Chloro-2-fluorobenzaldehydeHCID 4311764Sodium borohydrideHCID 668545511-(6-Fluoropyridin-3-yl)-pyrrolidin-3-ylamine hydrochloride

생성물 1

HCID 59860365(S)-4-Chloro-2-fluorobenzyl-[1-(6-fluoropyridin-3-yl)-pyrrolidin-3-yl]-amine

시약·촉매·용매 1

HCID 887Methanol용매2회

실험 절차

Dissolve 1-(6-fluoropyridin-3-yl)-pyrrolidin-3-ylamine hydrochloride (43 mg, 0.20 mmol) in methanol (1 mL). Add triethylamine (90 μL, 0.65 mmol) and 4-chloro-2-fluorobenzaldehyde (35 mg, 0.22 mmol), vortex and let sit overnight at room temperature. Add sodium borohydride (15 mg, 0.39 mmol) and let sit 1 h. Dilute the mixture with methanol and pour onto a column of Dowex® 50wx4-200 (1.5 g). Wash with methanol and discard the washing, then elute with 5% triethylamine in methanol. Concentrate to give the title compound as a residue. Dissolve the residue in methanol and add 1 N HCl in methanol (0.75 mL). Concentrate and dry in vacuum oven at 50° C. overnight to give the title compound as its hydrochloride salt (53 mg, 74%). 1H NMR (400 MHz, MeOH-d4) δ 7.63 (t, 1H, J=8.0 Hz), 7.58-7.57 (m, 1H), 7.45 (dd, 1H, J=9.6, 2.0 Hz), 7.40 (dd, 1H, J=8.0, 2.0 Hz), 7.36-7.32 (m, 1H), 7.00 (dd, 1H, J=8.8, 2.8 Hz), 4.44 (s, 2H), 4.21-4.15 (m, 1H), 3.74-3.61 (m, 3H), 3.42-3.36 (m, 1H), 2.68-2.60 (m, 1H), 2.38-2.29 (m, 1H), MS (ES): m/z=324 [M+H].

후처리

  1. washWash with methanol
  2. washelute with 5% triethylamine in methanol
  3. concentrationConcentrate

출처 및 근거

ORD 기록
ord-c0f009db6272446b88790e9c01b77045
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07868014B2

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