Triethylamine → (5r/s,6r/s)-n-(Cyanomethyl)-6-{[(4-fluorophenyl)sulfanyl]methyl}spiro[2.4]-heptane-5-carboxamide

HRID 2222918노트

반응식

HRID 2222918 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH:10]2[CH2:16][C:13]3([CH2:15][CH2:14]3)[CH2:12][CH:11]2[C:17]([OH:19])=O)=[CH:4][CH:3]=1.Cl.[NH2:21][CH2:22][C:23]#[N:24].F[P-](F)(F)(F)(F)F.N1([PH+](N2CCCC2)N2CCCC2)CCCC1.C(N(CC)CC)C>CN(C)C=O>[C:22]([CH2:23][NH:24][C:17]([CH:11]1[CH:10]([CH2:9][S:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:16][C:13]2([CH2:14][CH2:15]2)[CH2:12]1)=[O:19])#[N:21]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 11491918Aminoacetonitrile hydrochlorideHCID 22226026Tripyrrolidinophosphonium hexafluorophosphateHCID 69679911(5r/s,6r/s)-6-{[(4-Fluorophenyl)sulfanyl]-methyl}spiro[2.4]heptane-5-carboxylic acid

생성물 1

HCID 59711755(5r/s,6r/s)-n-(Cyanomethyl)-6-{[(4-fluorophenyl)sulfanyl]methyl}spiro[2.4]-heptane-5-carboxamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
0 °C

실험 절차

To (5R/S,6R/S)-6-{[(4-fluorophenyl)sulfanyl]methyl}spiro[2.4]heptane-5-carboxylic acid (59 mg, 0.21 mmol) was added aminoacetonitrile hydrochloride (30 mg, 0.32 mmol) and benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (120 mg, 0.23 mmol) and dimethylformamide (0.70 mL). The reaction mixture was cooled to 0° C. and triethylamine (90 PL, 0.65 mmol) was added. After stirring for 11 h, the reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated and washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and concentrated. Chromatography of the residue on silica gel with 35:65 ethyl acetate:hexanes provided the title compound as a of a colorless, waxy solid. 1H NMR (500 MHz, acetone-d6): δ=7.76 (1H, br s), 7.40 (2H, dd), 7.08 (2H, t), 4.22 (2H, d), 3.15 (1H, dd), 2.93 (1H, dd), 2.75 (1H, dd), 2.66 (1H, m), 1.90 (1H, dd), 1.86 (1H, dd), 1.50 (1H, dd), 0.45 (4H, m). MS [APCI, (M−H)−] m/z=317.0 amu.

후처리

  1. customthe reaction mixture was partitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with saturated sodium chloride aqueous solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-9977a5810db14d9b8e1e4156eeab6f8c
출처 데이터셋
uspto-grants-2008_05
특허 번호
US07371747B2

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