1,2-Dichloroethane → HCID 178522613, compound

HRID 518618Notes

Reaction equation

HRID 518618 reaction equation
[F:1][C:2]1[CH:35]=[CH:34][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:26]=[CH:25][C:24]([CH2:27][N:28]4[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]4)=[CH:23][C:12]=3[N:13]\2[C@@H:14]2[CH2:19][CH2:18][C@H:17]([C:20](O)=[O:21])[CH2:16][CH2:15]2)=[O:7])=[CH:4][CH:3]=1.[S:36]1[CH:40]=[CH:39][N:38]=[C:37]1[NH2:41].CN(C=O)C.C(Cl)CCl>CN(C)C1C=CN=CC=1.O.C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:26]=[CH:25][C:24]([CH2:27][N:28]4[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]4)=[CH:23][C:12]=3[N:13]\2[C@H:14]2[CH2:19][CH2:18][C@@H:17]([C:20](=[O:21])[NH:41][C:37]3[S:36][CH:40]=[CH:39][N:38]=3)[CH2:16][CH2:15]2)=[O:7])=[CH:34][CH:35]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 21552-AminothiazoleHCID 6228DimethylformamideHCID 178522614HCID 178522614, compound

Product 1

HCID 178522613HCID 178522613, compoundYield 46.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A round bottom flask under nitrogen atmosphere was charged with cis-4-((E)-2-(4-fluorobenzoylimino)-6-(piperidin-1-ylmethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylic acid (50 mg, 0.104 mmol), N,N-dimethylpyridin-4-amine (31.9 mg, 0.261 mmol), thiazol-2-amine (15.69 mg, 0.157 mmol), and DMF (2 mL). To this mixture was added EDC (40.1 mg, 0.209 mmol), and the reaction was stirred for 48 hours. The resulting mixture was diluted with water (10 mL) and DCM (30 mL). The organic layer was collected, dried over sodium sulfate and concentrated to afford a brown oil. The residual oil was purified by HPLC (10-70% ACN/H2O; 0.1% TFA) to afford (E)-4-fluoro-N-(6-(piperidin-1-ylmethyl)-1-(cis-4-(thiazol-2-ylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide (0.027 g, 46.1% yield). MS m/z=561.2 [M+H]. Calc'd for C30H33FN6O2S: 560.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23-1.36 (m, 1H) 1.36-1.48 (m, 2H) 1.50-1.60 (m, 4H) 1.68-1.84 (m, 2H) 1.86-2.01 (m, 2H) 2.26-2.37 (m, 2H) 2.40-2.50 (m, 3H) 2.75-2.90 (m, 2H) 2.98-3.10 (m, 1H) 3.63 (s, 2H) 4.77-5.08 (m, 1H) 7.18-7.24 (m, 1H) 7.24-7.32 (m, 2H) 7.36 (d, J=3.62 Hz, 1H) 7.52-7.59 (m, 2H) 7.66 (s, 1H) 8.30-8.42 (m, 2H) 12.21 (s, 1H) 12.83 (s, 1H).

Workup

  1. customThe organic layer was collected
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. customto afford a brown oil
  5. customThe residual oil was purified by HPLC (10-70% ACN/H2O; 0.1% TFA)

Sources & evidence

ORD record
ord-5533e3f6de0246478e8b02ef14b6d961
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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