Dicyclohexylcarbodiimide → HCID 86707932, compound

HRID 1396033Notes

Reaction equation

HRID 1396033 reaction equation
[CH2:1]([O:8][P:9]([O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([OH:29])=[O:28])=[CH:22][CH:21]=1)([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=1[C:38]([C:41]1[N:42]([C:50]2[CH:55]=[CH:54][C:53]([C:56]3[CH:61]=[C:60]([S:62]([CH3:65])(=[O:64])=[O:63])[C:59]([CH2:66]O)=[C:58]([F:68])[CH:57]=3)=[CH:52][C:51]=2[F:69])[CH:43]=[C:44]([C:46]([OH:49])([CH3:48])[CH3:47])[N:45]=1)([CH3:40])[CH3:39].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH2:12]([O:11][P:9]([O:19][C:20]1[CH:21]=[CH:22][C:23]([CH2:26][C:27]([O:29][CH2:66][C:59]2[C:60]([S:62]([CH3:65])(=[O:63])=[O:64])=[CH:61][C:56]([C:53]3[CH:54]=[CH:55][C:50]([N:42]4[CH:43]=[C:44]([C:46]([OH:49])([CH3:47])[CH3:48])[N:45]=[C:41]4[C:38]([C:32]4[C:33]([Cl:37])=[CH:34][CH:35]=[CH:36][C:31]=4[Cl:30])([CH3:40])[CH3:39])=[C:51]([F:69])[CH:52]=3)=[CH:57][C:58]=2[F:68])=[O:28])=[CH:24][CH:25]=1)([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 49787490Bms-852927HCID 57798931HCID 57798931, compound

Product 1

HCID 86707932HCID 86707932, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

4-Dimethylaminopyridine (0.19 g, 1.6 mmol) was added to a solution of 2-(4-(bis(benzyloxy)phosphoryloxy)phenyl)acetic acid (0.67 g, 1.6 mmol), 2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol (prepared in the manner described in PCT Publication No. WO 2010/138598, 0.4 g, 0.6 mmol), and N,N′-dicyclohexylcarbodiimide (0.37 g, 1.8 mmol) in CH2Cl2 (5 mL). The mixture was stirred at rt for 30 mins. After this time, the reaction mixture was filtered, and the organic solvents were removed under reduced pressure to yield the crude product. The crude product was purified by column chromatography using a mixture of CHCl3 and methanol (9:1) to afford (4′-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-4-(2-hydroxypropan-2-yl)-1H-imidazol-1-yl)-3,3′-difluoro-5-(methylsulfonyl)biphenyl-4-yl)methyl 2-(4-(bis(benzyloxy)phosphoryloxy)phenyl)acetate (0.4 g, 0.4 mmol, 60% yield). 1H NMR (400 MHz, CHCl3-d) δ 1.60 (s, 6H), 2.03 (s, 6H), 2.99 (s, 3H), 3.65 (s, 2H), 5.11 (d, J=8.4, 2H), 5.67 (s, 2H), 6.62 (s, 1H), 6.88 (t, J=7.6, 1H), 6.8-7.98 (m, 22H), 7.98 (s, 1H). LCMS: (Ascentis Express C18, 5×2.1 mm, 2.7 μm; Solvent A=2% MeCN: 98% H2O: 10 mM NH4COOH; Solvent B=98% MeCN: 2% H2O: 10 mM NH4COOH; gradient 0-100% B over 1.5 min) retention time: 2.38 min; LCMS (ES-API), m/z 1005.2 (M+H).

Workup

  1. customprepared in the manner
  2. filtrationAfter this time, the reaction mixture was filtered
  3. customthe organic solvents were removed under reduced pressure
  4. customto yield the crude product
  5. customThe crude product was purified by column chromatography
  6. additiona mixture of CHCl3 and methanol (9:1)

Sources & evidence

ORD record
ord-ed5504f7cea341f6b183c191467d6aa9
Source dataset
uspto-grants-2014_12
Patent number
US08901106B2

Reaction notes

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