Diisopropylethylamine → HCID 87181955, compound

HRID 1803307Notes

Reaction equation

HRID 1803307 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:8][C:9]1[N:10]=[CH:11][N:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[N:38]=[C:24]4[CH:25]([C:31]5[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=5)[CH2:26][C:27](=O)[CH2:28][CH2:29][N:23]4[N:22]=3)=[CH:16][C:15]=2[O:39][CH3:40])[CH:13]=1.Cl.[O:42]([NH2:44])[CH3:43].CCN(C(C)C)C(C)C>C(O)C.CCOC(C)=O>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:43][O:42]/[N:44]=[C:27]1\[CH2:26][CH:25]([C:31]2[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=2)[C:24]2[N:23]([N:22]=[C:21]([NH:20][C:17]3[CH:18]=[CH:19][C:14]([N:12]4[CH:13]=[C:9]([Cl:8])[N:10]=[CH:11]4)=[C:15]([O:39][CH3:40])[CH:16]=3)[N:38]=2)[CH2:29][CH2:28]\1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 66860172HCID 66860172, compound

Product 1

HCID 87181955HCID 87181955, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-9-(4-fluorophenyl)-8,9-dihydro-5H-[1,2,4]triazolo[1,5-a]azepin-7(6H)-one (100 mg, 0.214 mmol, from example 137) in ethanol (1.1 mL) was added methoxylamine hydrochloride (35.8 mg, 0.428 mmol) and DIPEA (112 μL, 0.643 mmol). The resulting mixture was stirred at rt for 16 h. The reaction mixture was diluted with EtOAc (10 mL), washed with water (5 mL), brine (5 mL), dried over Mg SO4, filtered and concentrated in vacuo. The crude product was purified using reverse phase preparatory HPLC (MeOH/water/trifluoroacetic acid) to afford the TFA salt of the titled compound as a mixture of E/Z isomers (76.7 mg, 56% yield). LC-MS (M+H)+ 496.2. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 9.52-9.79 (1 H, m), 8.02 (1 H, s), 7.25-7.36 (1 H, m), 7.05-7.25 (7 H, m), 4.46-4.73 (3 H, m), 3.81-3.97 (6 H, m), 2.95-3.24 (3 H, m), 2.84 (1 H, t, J=5.8 Hz).

Workup

  1. washwashed with water (5 mL), brine (5 mL)
  2. dry with materialdried over Mg SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified

Sources & evidence

ORD record
ord-8a2f5e51303746d58edf0f78b82bf9fe
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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