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 1891465ノート

反応式

HRID 1891465 の反応式
[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]

参加物

7

反応物 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

生成物 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-hydroxyacetamide収率 50%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

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.

後処理

  1. customPrepared
  2. customThe crude reaction mixture

出典と根拠

ORDレコード
ord-6165bf739fee4bffaf47be3bee018e70
出典データセット
uspto-grants-2013_08
特許番号
US08507538B2

反応ノート

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