Ethylamine hydrochloride → (1S,2R)-4'-(4-Chlorophenyl)-N-ethyl-2',3',9'-trimethylspiro[cyclopropane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine]-2-carboxamide

HRID 1772338노트

반응식

HRID 1772338 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[C:15]([CH3:19])=[C:16]([CH3:18])[S:17][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]3[C@@:10]3([CH2:25][C@H:24]3[C:26](O)=[O:27])[N:9]=2)=[CH:4][CH:3]=1.[CH:29]([N:32](CC)C(C)C)(C)[CH3:30].Cl.C(N)C.C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[C:15]([CH3:19])=[C:16]([CH3:18])[S:17][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]3[C@@:10]3([CH2:25][C@H:24]3[C:26]([NH:32][CH2:29][CH3:30])=[O:27])[N:9]=2)=[CH:4][CH:3]=1

참가 물질

7

반응물 5

HCID 11198Ethylamine hydrochlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57404934(1S,2R)-4'-(4-Chlorophenyl)-2',3',9'-trimethylspiro[cyclopropane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine]-2-carboxylic acid2회

생성물 1

HCID 67951116(1S,2R)-4'-(4-Chlorophenyl)-N-ethyl-2',3',9'-trimethylspiro[cyclopropane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine]-2-carboxamide수율 35.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of crude (1S,2R)-4′-(4-chlorophenyl)-2′,3′,9′-trimethylspiro[cyclopropane-1,6′-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine]-2-carboxylic acid (Compound 228; 0.09 g, 0.218 mmol) in DCM (2.4 mL) was added N,N-diisopropylethylamine (0.190 ml, 1.090 mmol), ethylamine hydrochloride (0.071 g, 0.872 mmol) and HOBt (0.017 g, 0.109 mmol). The mixture was stirred for 10 min at rt (still heterogeneous) before HATU (0.166 g, 0.436 mmol) was added, still at rt. After 20 min, the reaction was filtered on a pad of silica gel. The silica gel was successively rinsed with EtOAc/hexane (5:5) to (10:0) and DCM/MeOH (9:1). The filtrate was concentrated to dryness, and the residue was purified by reverse phase chromatography to give the desired product as an off-white solid (34 mg). LRMS (M+H)+: 440 m/z. 1H NMR (major conformer reported only) (400 MHz, DMSO-d6) δ 8.36 (br. s., 1H), 7.37-7.54 (m, 4H), 2.89-3.01 (m, 1H), 2.69-2.82 (m, 1H), 2.62 (s, 3H), 2.36 (s, 3H), 2.07 (dd, J=5.15, 8.81 Hz, 1H), 1.92 (t, J=6.40 Hz, 1H), 1.78 (t, J=8.00 Hz, 1H), 1.43 (s, 3H), 0.84 (t, J=7.10 Hz, 3H).

후처리

  1. additionwas added, still at rt
  2. filtrationthe reaction was filtered on a pad of silica gel
  3. washThe silica gel was successively rinsed with EtOAc/hexane (5:5) to (10:0) and DCM/MeOH (9:1)
  4. concentrationThe filtrate was concentrated to dryness
  5. customthe residue was purified by reverse phase chromatography

출처 및 근거

ORD 기록
ord-041e7e17c41b4cdc9adeaebab3fb00c0
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09249161B2

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