1,2-Dichloroethane → HCID 178494981, compound

HRID 1254381Notes

Reaction equation

HRID 1254381 reaction equation
[C:1]([NH:3][C:4]([NH:6][C@@H:7]([CH2:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)[CH2:8][N:9]([CH3:19])[C:10]([O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[O:11])=S)#[N:2].Cl[C:28]1[CH:29]=[C:30]([C@:34]([C@@H:42]2[CH2:47][CH2:46][CH2:45][NH:44][CH2:43]2)([OH:41])[CH2:35][CH2:36][CH2:37][CH2:38][O:39][CH3:40])[CH:31]=[CH:32][CH:33]=1.C(Cl)CCl>CN(C=O)C.CCOCC>[C:1]([N:3]=[C:4]([N:44]1[CH2:45][CH2:46][CH2:47][C@@H:42]([C@:34]([OH:41])([C:30]2[CH:29]=[CH:28][CH:33]=[CH:32][CH:31]=2)[CH2:35][CH2:36][CH2:37][CH2:38][O:39][CH3:40])[CH2:43]1)[NH:6][C@@H:7]([CH2:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)[CH2:8][N:9]([CH3:19])[C:10]([O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[O:11])#[N:2]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 59382814(S)-1-(3-chlorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-olHCID 866530841-cyano-3-((S)-3-cyclohexyl-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)thiourea

Product 1

HCID 178494981HCID 178494981, compoundYield 38.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 1-cyano-3-((S)-3-cyclohexyl-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)thiourea (230 mg, 0.58 mmol) and (S)-1-(3-chlorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol (180 mg, 0.58 mmol) in DMF (5 mL) was added EDC (0.17 g, 0.87 mmol). The mixture was stirred for 16 h at rt, diluted with ether (175 mL) and washed with 5% aq HCl (2×50 mL) and brine (50 mL). The combined aqueous washes were back extracted with ether. The combined ether extracts were concentrated to afford crude product (290 mg). The mixture was purified by prep HPLC to afford (3R)—N′-cyano-N-((S)-3-cyclohexyl-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)-3-((S)-1-hydroxy-5-methoxy-1-phenylpentyl)piperidine-1-carboxamidine (145 mg, 37%).

Workup

  1. washwashed with 5% aq HCl (2×50 mL) and brine (50 mL)
  2. extractionThe combined aqueous washes were back extracted with ether
  3. concentrationThe combined ether extracts were concentrated
  4. customto afford crude product (290 mg)
  5. customThe mixture was purified by prep HPLC

Sources & evidence

ORD record
ord-750818732a834778b01446eae5573fb0
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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