1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86613043, compound

HRID 1874173Notes

Reaction equation

HRID 1874173 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@:15]([NH:30][C:31](=[O:39])[NH:32][C:33]2([C:36]([OH:38])=O)[CH2:35][CH2:34]2)([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:5]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:7]=1.C1(C2C=CC=CC=2)C=CC=CC=1.[C:52]1([P:58](=[CH:60][C:61]#[N:62])=[O:59])[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1.CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:23]1([C:15]2[CH:16]=[CH:17][CH:22]=[CH:21][CH:20]=2)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1.[C:61]([C:60](=[P:58]([C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)=[O:59])[C:36]([C:33]1([NH:32][C:31]([NH:30][C@@:15]([C:4]2[CH:5]=[C:6]([O:8][C:9]([F:13])([F:14])[CH:10]([F:11])[F:12])[CH:7]=[C:2]([F:1])[CH:3]=2)([C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[O:39])[CH2:34][CH2:35]1)=[O:38])#[N:62]

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 59459494HCID 59459494, compoundHCID 86613045HCID 86613045, compound

Product 1

HCID 86613043HCID 86613043, compoundYield 81.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-1-(3-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)ureido)-cyclopropanecarboxylic acid (84 mg, 0.153 mmol), prepared by the method described in Procedure 30, in DCM (0.5 mL) was added 2-(phenylphosphinylidene)acetonitrile compound with biphenyl (1:1) (51 mg, 0.168 mmol), EDCI (32 mg, 0.168 mmol) and DMAP (3 mg, 0.024 mmol). The reaction mixture was stirred at room temperature for 4.5 h, concentrated under reduced pressure and purified by ISCO chromatography (12 g column, eluting with 0-100% hexane/EtOAc) to yield (R)-1-(1-(2-cyano-2-(phenylphosphinylidene)acetyl)cyclopropyl)-3-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)urea compound with biphenyl (1:1) as a white solid (53 mg, 42% yield). LCMS: RT=3.49 min [M+H] 836.4 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 50-100% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm); 1H NMR (400 MHz, CDCl3) ppm 0.78-1.00 (m, 2H), 1.34-1.49 (m, 2H), 3.79-3.95 (m, 2H), 5.62-5.98 (m, 3H), 6.67-6.94 (m, 7H), 6.98-7.20 (m, 5H), 7.37-7.66 (m, 15H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. custompurified by ISCO chromatography (12 g column, eluting with 0-100% hexane/EtOAc)

Sources & evidence

ORD record
ord-b22cad9660d34c59890f2c01b2001047
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

Loading…