HOAt → (2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-methoxythiazole-5-carboxamido)-2-methylpentanoate

HRID 2384109노트

반응식

HRID 2384109 반응식
[CH3:1][O:2][C:3]1[S:4][C:5]([C:8]([OH:10])=O)=[CH:6][N:7]=1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:34][C@H:35]([CH2:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)=[CH:47][CH:46]=1)[CH2:36][C@@H:37]([CH3:43])[C:38]([O:40][CH2:41][CH3:42])=[O:39]>CN(C=O)C>[C:48]1([C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:47]=[CH:46][C:45]([CH2:44][C@@H:35]([NH:34][C:8]([C:5]2[S:4][C:3]([O:2][CH3:1])=[N:7][CH:6]=2)=[O:10])[CH2:36][C@@H:37]([CH3:43])[C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:50][CH:49]=1

참가 물질

6

반응물 4

HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 164948972-Methoxy-1,3-thiazole-5-carboxylic acidHCID 25017086(2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochloride

생성물 1

HCID 59608216(2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-methoxythiazole-5-carboxamido)-2-methylpentanoate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 2-methoxythiazole-5-carboxylic acid (101 mg, 0.64 mmol) in DMF (6 mL) is added HOAt (107 mg, 0.58 mmol), EDCl (133 mg, 0.69 mmol), and TEA (0.48 mL, 3.47 mmol). The crude is stirred at room temperature for 15 mins. To this crude is added (2R,4S)-ethyl 4-amino-5-(biphenyl-4-yl)-2-methylpentanoate hydrochloride salt. The crude is stirred at room temperature for overnight. The crude is quenched with 1 N HCl and water, diluted in EtOAc. The organic layer is washed with brine, dried over MgSO4, filtered, and concentrated. The residue is purified via flash column chromatography using 30% EtOAc/heptane to 70% EtOAc/heptane to give (2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-methoxythiazole-5-carboxamido)-2-methylpentanoate (170 mg). HPLC retention time 1.94 minutes (condition A); MS 453.3 (M+1); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.18 (d, J=7.1 Hz, 3H), 1.23 (t, J=7.1 Hz, 3H), 1.71 (ddd, J=14.0, 9.9, 3.9 Hz, 1H), 1.88-2.04 (m, 1H), 2.56-2.73 (m, 1H), 2.78-2.96 (m, 1H), 2.96-3.09 (m, 1H), 4.09 (s, 3H), 4.09-4.18 (m, 2H), 4.30-4.47 (m, 1H), 6.15 (d, J=8.1 Hz, 1H), 7.27 (d, J=6.8 Hz, 2H), 7.29-7.36 (m, 1H), 7.42 (t, J=7.6 Hz, 2H), 7.49 (s, 1H), 7.53 (d, J=8.1 Hz, 2H), 7.57 (d, J=7.3 Hz, 2H).

후처리

  1. stirringThe crude is stirred at room temperature for overnight
  2. customThe crude is quenched with 1 N HCl and water
  3. additiondiluted in EtOAc
  4. washThe organic layer is washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is purified via flash column chromatography

출처 및 근거

ORD 기록
ord-8ae0bcb35f75465594fc59dbfdcf107f
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08263629B2

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