1,2-Dichloroethane → (S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxyacetamide

HRID 1891465노트

반응식

HRID 1891465 반응식
[OH:1][CH2:2][C:3]([OH:5])=O.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.Cl.[NH2:30][C@@H:31]1[C:39]2[C:34](=[C:35]([C:40]3[S:44][C:43]([C:45]4[CH:46]=[CH:47][C:48]([O:53][CH:54]([CH3:56])[CH3:55])=[C:49]([CH:52]=4)[C:50]#[N:51])=[N:42][N:41]=3)[CH:36]=[CH:37][CH:38]=2)[CH2:33][CH2:32]1>CN(C=O)C>[C:50]([C:49]1[CH:52]=[C:45]([C:43]2[S:44][C:40]([C:35]3[CH:36]=[CH:37][CH:38]=[C:39]4[C:34]=3[CH2:33][CH2:32][C@@H:31]4[NH:30][C:3](=[O:5])[CH2:2][OH:1])=[N:41][N:42]=2)[CH:46]=[CH:47][C:48]=1[O:53][CH:54]([CH3:56])[CH3:55])#[N:51]

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 757Glycolic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67193845(S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride

생성물 1

HCID 53233216(S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxyacetamide수율 50%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

Prepared using General Procedure 6. A solution of 2-hydroxyacetic acid (4 mg, 0.05 mmol), HOBt (8.8 mg, 0.06 mmol), EDC (12.5 mg, 0.06 mmol) and DIEA (15 mg, 0.11 mmol) in DMF (1 mL) was stirred for 30 min before the addition of (S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 4 in DMF (0.5 mL). The reaction mixture was stirred at room temperature overnight. The crude reaction mixture was preparative HPLC to produce 10 mg (50%) of (S)-N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl)-2-hydroxyacetamide 7 as white solid. LCMS-ESI (m/z) calculated for: C23H22N4O3S: 434.1; found 435.1 [M+H]+, tR=3.11 min. 1H NMR (400 MHz, CDCl3) δ 8.19 (dd, J=8.9, 2.3 Hz, 1H), 8.12 (d, J=2.2 Hz, 1H), 7.79 (d, J=7.6 Hz, 1H), 7.42 (d, J=7.5 Hz, 1H), 7.34 (t, J=7.6 Hz, 1H), 7.09 (d, J=9.0 Hz, 1H), 6.85 (d, J=8.5 Hz, 1H), 5.71-5.46 (m, 1H), 4.76 (dt, J=12.2, 6.1 Hz, 1H), 4.21 (s, 2H), 3.46 (ddd, J=17.0, 8.7, 3.6 Hz, 1H), 3.30-3.09 (m, 1H), 2.69 (ddd, J=16.6, 8.3, 4.0 Hz, 1H), 2.08-1.80 (m, 2H), 1.46 (d, J=6.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 167.44, 166.23, 162.20, 145.53, 142.82, 133.89, 133.79, 129.53, 128.28, 127.20, 126.93, 123.12, 116.03, 114.38, 104.22, 73.06, 62.72, 54.46, 33.91, 31.98, 22.24.

후처리

  1. customPrepared
  2. customThe crude reaction mixture

출처 및 근거

ORD 기록
ord-6165bf739fee4bffaf47be3bee018e70
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08507538B2

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