Diisopropylethylamine → HCID 68485564, compound

HRID 1875022Notes

Reaction equation

HRID 1875022 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[Cl-].FC(F)(F)C(O)=O.[NH2:36][C:37]1[CH:38]=[C:39]2[C:43](=[CH:44][CH:45]=1)[NH:42][C:41]([C:46]([NH:48][CH2:49][C:50]1[CH:55]=[CH:54][C:53]([Cl:56])=[C:52]([O:57][C:58]3[CH:63]=[C:62]([C:64]#[N:65])[CH:61]=[C:60]([Cl:66])[CH:59]=3)[C:51]=1[F:67])=[O:47])=[CH:40]2.[CH3:68][C:69]([O:72][C:73]([N:75]1[CH2:80][CH2:79][CH:78]([C:81](O)=[O:82])[CH2:77][CH2:76]1)=[O:74])([CH3:71])[CH3:70].C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:56][C:53]1[CH:54]=[CH:55][C:50]([CH2:49][NH:48][C:46]([C:41]2[NH:42][C:43]3[C:39]([CH:40]=2)=[CH:38][C:37]([NH:36][C:81]([CH:78]2[CH2:79][CH2:80][N:75]([C:73]([O:72][C:69]([CH3:71])([CH3:70])[CH3:68])=[O:74])[CH2:76][CH2:77]2)=[O:82])=[CH:45][CH:44]=3)=[O:47])=[C:51]([F:67])[C:52]=1[O:57][C:58]1[CH:63]=[C:62]([C:64]#[N:65])[CH:61]=[C:60]([Cl:66])[CH:59]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 866448845-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetateHCID 131720136BOP chloride

Product 1

HCID 68485564HCID 68485564, compoundYield 41.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

BOP chloride (0.079 g, 0.309 mmol) was added to a solution of 5-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetate (0.060 g, 0.103 mmol), 1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinecarboxylic acid (0.0236 g, 0.103 mmol) and diisopropylethylamine (0.090 mL, 0.514 mmol) in DMF (1 mL). The mixture was stirred at room temperature for 1 hr. The reaction mixture was extracted with ethyl acetate and water. The organic layer was washed with water, dried over sodium sulfate and concentrated. The residue was purified by flash chromatography with hexane:ethyl acetate to give the title compound (0.029 g, 41%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.50 (br. s., 1H), 9.72 (br. s., 1H), 8.95 (br. s., 1H), 7.95 (s, 1H), 7.78 (s, 1H), 7.41-7.52 (m, 2H), 7.36 (t, 1H), 7.25-7.32 (m, 1H), 7.21 (d, 1H), 7.06 (br. s., 1H), 4.52 (d, 2H), 3.85-4.17 (m, 2H), 2.58-2.94 (m, 2 H), 1.63-1.85 (m, 2H), 1.41-1.53 (m, 2H), 1.36 (s, 9H). ES MS: m/z 680 (M+1).

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate and water
  2. washThe organic layer was washed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography with hexane

Sources & evidence

ORD record
ord-3ce58cae1e89467c8328071a8527ec6d
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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