Triethylamine → HCID 178511967, compound

HRID 1020921Notes

Reaction equation

HRID 1020921 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:30]=[CH:31][C:32]=1F)[C:6]([NH:8][C@H:9]([C:17]1[NH:18][CH:19]=[C:20]([C:22]2[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[CH:24][CH:23]=2)[N:21]=1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])#[N:2].C(C1C=C(C=CC=1F)C(O)=O)#N.C([N:48](CC)CC)C.F[P-](F)(F)(F)(F)F.[N:60]1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=[N:61]1>C1COCC1.O>[NH2:2][C:1]1[C:3]2[C:32](=[CH:31][CH:30]=[C:5]([C:6]([NH:8][C@H:9]([C:17]3[NH:18][CH:19]=[C:20]([C:22]4[CH:27]=[CH:26][C:25]([C:28](=[NH:48])[NH2:29])=[CH:24][CH:23]=4)[N:21]=3)[CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[O:7])[CH:4]=2)[NH:61][N:60]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27739323-Cyano-4-fluorobenzoic acidHCID 178509599HCID 178509599, compound

Product 1

HCID 178511967HCID 178511967, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Part B: 3-Cyano-N—{(S)-1-[4-(4-cyano-phenyl)-1H-imidazol-2-yl]-2-phenyl-ethyl}-4-fluoro-benzamide: A mixture of the compound of Example 176 Part A (100 mg, 0.28 mmol), 3-cyano-4-fluorobenzoic acid (46 mg, 0.28 mmol), triethylamine (0.085 mL, 0.61 mmol) and BOP (0.18 g, 0.4 mmol) in THF (5 mL) was stirred at rt overnight under N2. Reaction mixture was diluted with water and extracted 3× with EtOAc. The combined extracts were washed with sat'd. NaHCO3 and brine and then dried over anhydrous Na2SO4, filtered and evaporated. Chromatography on silica gel (hexane/EtOAc) provided the amide product (88 mg, 72%). 1H NMR (500 MHz, CDCl3) δ 3.41 (dd, J=13.75, 7.15 Hz, 1H) 3.58 (dd, J=13.47, 7.97 Hz, 1H) 5.33 (q, J=7.70 Hz, 1H) 7.01-7.09 (m, 1H) 7.18-7.37 (m, 7H) 7.66 (d, J=8.25 Hz, 2H) 7.85 (d, J=8.25 Hz, 2H) 7.89-7.96 (m, 1H) 7.95-8.03 (m, 1H) 9.74 (s, 1H). m/z 436.1 (M+H)+.

Workup

  1. customReaction mixture
  2. extractionextracted 3× with EtOAc
  3. washThe combined extracts were washed with sat'd
  4. dry with materialNaHCO3 and brine and then dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-ba0fb6468f544d59b8f3705cd3c4a8fa
Source dataset
uspto-grants-2014_05
Patent number
US08716492B2

Reaction notes

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