1,2-Dichloroethane → 4-[2-[1-[4-[N'-(2-fluorophenyl)ureido)-3-methoxyphenylacetyl]-2-pyrrolidinyl]ethynyl]benzoic Acid

HRID 350358Notes

Reaction equation

HRID 350358 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:23])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([OH:20])=O)=[CH:13][C:12]=1[O:21][CH3:22].C([O:26][C:27]([C:29]1[CH:34]=[CH:33][C:32]([C:35]#[C:36][CH:37]2[CH2:41][CH2:40][CH2:39][NH:38]2)=[CH:31][CH:30]=1)=[O:28])C.C(Cl)CCl.Cl>CN(C1C=CN=CC=1)C.CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:23])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([N:38]2[CH2:39][CH2:40][CH2:41][CH:37]2[C:36]#[C:35][C:32]2[CH:33]=[CH:34][C:29]([C:27]([OH:28])=[O:26])=[CH:30][CH:31]=2)=[O:20])=[CH:13][C:12]=1[O:21][CH3:22]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 23511825HCID 23511825, compoundHCID 235119142-(2-(4-Ethoxycarbonylphenyl)ethynyl)pyrrolidine

Product 1

HCID 98493854-[2-[1-[4-[N'-(2-fluorophenyl)ureido)-3-methoxyphenylacetyl]-2-pyrrolidinyl]ethynyl]benzoic Acid

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-[N′-(2-fluorophenyl)ureido]-3-methoxyphenylacetic acid (255 mg, 0.8 mmol), 2-[2-(4-ethoxycarbonylphenyl)ethynyl]pyrrolidine (195 mg, 0.8 mmol), EDC (230 mg, 1.2 mmol), DMAP (98 mg, 0.8 mmol) in DMF (20 mL) was stirred overnight. The reaction mixture was poured into 1 N HCl and the resulting precipitate was collected with suction and dissolve in CHCl3. The solution was dried over MgSO4 and evaporated. The residue was chromatographed on silica gel with CHCl3-MeOH (100:1, v/v) as eluent to give the desired compound, which was dissolved in THF (8 mL). 0.25 N NaOH (8 mL) was added to this solution and the resulting mixture was stirred overnight. The mixture was poured into 1 N HCl and extracted with CHCl3. The extract was washed with brine, dried over MgSO4, and evaporated. The residue was recrystallized from CHCl3-n-hexane to give 144 mg (37%) 33 as a pale yellow crystalline powder. mp 152–155 (d); 1H-NMR (DMSO-d6) δ 1.92–2.27 (4 H, m), 2.50 (2 H, s), 3.33–3.78 (2 H, m), 3.80 and 3.82 (total 3 H, s, each), 4.88–5.12 (1 H, m), 6.77–7.24 and 7.99–8.20 (total 7 H, m), 7.48 and 7.52 (2 H, d, J=8.3 Hz, each), 7.91 (2H, d, J=8.3 Hz), 8.72 (1H, s), 9.18 (1H, s), 13.11 (1H, br-s); MS (FAB) m/z 516 (M++1); Anal. Calcd for C29H26N3O5F.2H2O: C, 63.15; H, 5.48; N, 7.62. Found: C, 63.58; H, 5.15; N, 7.22.

Workup

  1. customthe resulting precipitate was collected with suction
  2. dissolutiondissolve in CHCl3
  3. dry with materialThe solution was dried over MgSO4
  4. customevaporated
  5. customThe residue was chromatographed on silica gel with CHCl3-MeOH (100:1

Sources & evidence

ORD record
ord-ec093d37d027475fabb79c662a1415e7
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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