1,2-Dichloroethane → HCID 46853084, compound

HRID 2199704Notes

Reaction equation

HRID 2199704 reaction equation
[Br:1][C:2]1[C:10]2[S:9][CH:8]=[C:7]([CH:11]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)[C@@H:12]([C:16]3[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=3)[CH2:13][CH2:14][CH3:15])[C:6]=2[CH:5]=[C:4]([CH3:32])[CH:3]=1.[N:33]1[NH:34][N:35]=[N:36][C:37]=1[CH2:38][NH2:39].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(#N)C>[Br:1][C:2]1[C:10]2[S:9][CH:8]=[C:7]([CH:11]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)[C@@H:12]([C:16]3[CH:24]=[CH:23][C:19]([C:20]([NH:39][CH2:38][C:37]4[N:33]=[N:34][NH:35][N:36]=4)=[O:21])=[CH:18][CH:17]=3)[CH2:13][CH2:14][CH3:15])[C:6]=2[CH:5]=[C:4]([CH3:32])[CH:3]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5146781(1H-tetrazol-5-ylmethyl)amineHCID 58513017HCID 58513017, compound

Product 1

HCID 46853084HCID 46853084, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 4-{(1S)-1-[(7-bromo-5-methyl-1-benzothien-3-yl)(4-chlorophenyl)methyl]butyl}benzoic acid (EXAMPLE 3, Step A, 20.0 mg, 0.038 mmol), 1-(2H-tetrazol-5-yl)methanamine (10.9 mg, 0.110 mmol), EDC (22.0 mg, 0.110 mmol), HOBt (17.0 mg, 0.110 mmol) and DIEA (0.050 mL, 0.29 mmol) in DMF (1 mL) was heated at 65° C. for 12 hours. The mixture was allowed to cool to RT, diluted with acetonitrile, then purified by preparative reverse-phase HPLC eluting with 38-100% acetonitrile/water+0.1% TFA. Following lyophilization, this afforded the title compound as a white solid. 1H NMR (500 MHz, d6-DMSO) δ 9.04 (br, 1H); 7.96 (s, 1H); 7.84 (s, 1H); 7.67 (d, J=8 Hz, 2H); 7.64 (d, J=8 Hz, 2H); 7.52 (d, J=8 Hz, 2H); 7.39 (d, J=8.5 Hz, 2H); 7.35 (br, 1H); 4.84 (d, J=11.5 Hz, 1H); 4.67 (d, J=5.5 Hz, 2H); 3.74 (t, J=12 Hz, 1H); 2.40 (s, 3H); 1.44-1.52 (m, 1H); 1.24-1.32 (m, 1H); 0.91 (q, J=7.5 Hz, 2H); 0.67 (t, J=7 Hz, 3H). LC2: 2.63 min. (M+H)+ 608.

Workup

  1. temperatureto cool to RT
  2. custompurified by preparative reverse-phase HPLC
  3. washeluting with 38-100% acetonitrile/water+0.1% TFA

Sources & evidence

ORD record
ord-fe9cf3ca8eb340a48910218d5b7093aa
Source dataset
uspto-grants-2016_06
Patent number
US09359339B2

Reaction notes

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