3-Chloro-5-fluorobenzonitrile → HCID 58560983, compound

HRID 2408154Notes

Reaction equation

HRID 2408154 reaction equation
CC(C)([O-:4])C.[Na+].[Cl:7][C:8]1[CH:9]=[C:10]([CH:13]=[C:14](F)[CH:15]=1)[C:11]#[N:12].[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C@H:24]([OH:46])[C@@H:25]([C:32]2[CH:45]=[CH:44][C:35]([C:36]([NH:38][CH2:39][CH2:40][C:41]([OH:43])=[O:42])=[O:37])=[CH:34][CH:33]=2)[CH2:26][CH2:27][C:28]([F:31])([F:30])[F:29])=[CH:20][CH:19]=1.CC(C1NC(=O)C(CCSC)NC(=O)C(NC(C(NC(C(NC(C(NC(C(N)CC(O)=O)=O)C(O)C)=O)CCSC)=O)CCCNC(N)=N)=O)CSSCC(C(NC(C(NC(C(NC(C(O)=O)C(C)C)=O)CCC(O)=O)=O)CC2C3C(=CC=CC=3)NC=2)=O)NC(=O)C2N(CCC2)C(=O)C(CCCNC(N)=N)NC(=O)C(CC2C=CC(O)=CC=2)NC(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC1=O)C>CN(C=O)C.CCOC(C)=O>[NH2:12][C:11]([C:10]1[CH:13]=[C:14]([CH:15]=[C:8]([Cl:7])[CH:9]=1)[O:46][C@@H:24]([C:21]1[CH:22]=[CH:23][C:18]([Cl:17])=[CH:19][CH:20]=1)[C@@H:25]([C:32]1[CH:45]=[CH:44][C:35]([C:36]([NH:38][CH2:39][CH2:40][C:41]([OH:43])=[O:42])=[O:37])=[CH:34][CH:33]=1)[CH2:26][CH2:27][C:28]([F:31])([F:30])[F:29])=[O:4]

Participants

7

Reactant 4

HCID 27348413-Chloro-5-fluorobenzonitrileHCID 16167454Melanin-concentrating hormoneHCID 23676156Sodium t-butoxideHCID 86660369HCID 86660369, compound

Product 1

HCID 58560983HCID 58560983, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium tert-butoxide (92 mg, 0.96 mmol) was added to a solution of 3-chloro-5-fluorobenzonitrile (67.9 mg, 0.359 mmol) and N-(4-{(1R)-1-[(R)-(4-chlorophenyl)(hydroxy)methyl]-4,4,4-trifluorobutyl}benzoyl)-β-alanine (prepared using the procedures from INTERMEDIATE 1 and the saponification step of EXAMPLE 1, 100 mg, 0.239 mmol) in DMF (3 mL), then the resulting brown mixture was stirred at 80° C. for 16 hours. The mixture was diluted with EtOAc, then washed with 2 N HCl(aq), then washed twice with water. The organic layer was then concentrated, and the resulting yellow residue was purified by reverse phase HPLC eluting with 30-100% MeCN/water+0.1% TFA. Following lyophilization, this afforded the title compound. LC3 3.35 min. (M+H)+ 577.

Workup

  1. customprepared
  2. washwashed with 2 N HCl(aq)
  3. washwashed twice with water
  4. concentrationThe organic layer was then concentrated
  5. customthe resulting yellow residue was purified by reverse phase HPLC
  6. washeluting with 30-100% MeCN/water+0.1% TFA

Sources & evidence

ORD record
ord-5885e5fa21b64351a9287605657d85bc
Source dataset
uspto-grants-2014_08
Patent number
US08809579B2

Reaction notes

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