Triethylamine → HCID 68159047, compound

HRID 403190Notes

Reaction equation

HRID 403190 reaction equation
[F:1][C:2]([F:26])([F:25])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH:21]4[CH2:23][CH:22]4[NH2:24])=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.CCN(CC)CC.Cl[C:35]([O:37][C:38]1[C:43]([CH3:44])=[CH:42][C:41]([CH3:45])=[CH:40][C:39]=1[CH3:46])=[O:36]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[F:26][C:2]([F:1])([F:25])[O:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH:21]4[CH2:23][CH:22]4[NH:24][C:35](=[O:36])[O:37][C:38]4[C:43]([CH3:44])=[CH:42][C:41]([CH3:45])=[CH:40][C:39]=4[CH3:46])=[CH:17][CH:16]=3)=[N:11]2)=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 11106338HCID 11106338, compoundHCID 68158720HCID 68158720, compound

Product 1

HCID 68159047HCID 68159047, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

2-{4-[1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]phenyl}cyclopropylamine (46.0 mg, 0.13 mmol, 1.0 equiv) was dissolved in CH2Cl2 (0.55 mL) under N2. 4-Dimethylaminopyridine (DMAP; 0.8 mg, 0.006 mmol, 0.05 equiv) and Et3N (27 μL, 0.19 mmol, 1.5 equiv) were added, followed by mesityl chloroformate prepared above (33 mg, 0.17 mmol, 1.2 equiv). The reaction was stirred for 5 min and was then quenched with NaHCO3 (aq). The layers were separated, and the aqueous layer was extracted twice more with CH2Cl2. The combined organic extracts were concentrated, and the crude product was purified by silica gel chromatography (EtOAc-hexanes gradient) to afford the title compound as a white solid (53.0 mg, 79%): mp 199-202° C.; 1H NMR (400 MHz, CDCl3, data for major rotamer) δ 8.54 (s, 1H), 8.08 (d, J=8.3 Hz, 2H), 7.78 (d, J=9.0 Hz, 2H), 7.39 (d, J=0.7 Hz, 2H), 7.32-7.21 (m, 2H), 6.86 (s, 2H), 5.71-5.36 (m, 0.7H), 5.22-4.82 (m, 0.3H), 3.09-2.81 (m, 1H), 2.26 (s, 4H), 2.17 (s, 6H), 1.43-1.26 (m, 2H); ESIMS m/z 523 (M+H).

Workup

  1. customprepared above (33 mg, 0.17 mmol, 1.2 equiv)
  2. customwas then quenched with NaHCO3 (aq)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted twice more with CH2Cl2
  5. concentrationThe combined organic extracts were concentrated
  6. customthe crude product was purified by silica gel chromatography (EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-065e2968b13a491599309642b980c802
Source dataset
uspto-grants-2014_06
Patent number
US08748340B2

Reaction notes

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