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 1891465Notes

Reaction equation

HRID 1891465 reaction equation
[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]

Participants

7

Reactant 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

Product 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-hydroxyacetamideYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

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.

Workup

  1. customPrepared
  2. customThe crude reaction mixture

Sources & evidence

ORD record
ord-6165bf739fee4bffaf47be3bee018e70
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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