Triethylamine → HCID 86714626, compound

HRID 1409323Notes

Reaction equation

HRID 1409323 reaction equation
[Br:1][CH2:2][C:3]1[O:7][N:6]=[C:5]([C:8]([OH:10])=O)[CH:4]=1.C1(N=C=NC2CCCCC2)CCCCC1.[NH2:26][C@@H:27]([CH3:44])[CH2:28][N:29]1[CH:33]=[CH:32][C:31]([C:34]2[CH:41]=[C:40]([F:42])[C:37]([C:38]#[N:39])=[C:36]([Cl:43])[CH:35]=2)=[N:30]1.C(N(CC)CC)C>C(Cl)Cl.C1COCC1>[Br:1][CH2:2][C:3]1[O:7][N:6]=[C:5]([C:8]([NH:26][C@@H:27]([CH3:44])[CH2:28][N:29]2[CH:33]=[CH:32][C:31]([C:34]3[CH:41]=[C:40]([F:42])[C:37]([C:38]#[N:39])=[C:36]([Cl:43])[CH:35]=3)=[N:30]2)=[O:10])[CH:4]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 10868Dicyclohexylcarbodiimide2×HCID 133710205-(Bromomethyl)-1,2-oxazole-3-carboxylic acid2×HCID 67170587(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile

Product 1

HCID 86714626HCID 86714626, compoundYield 38.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

5-(Bromomethyl)isoxazole-3-carboxylic acid (0.718 mmol, 0.148 g) was dissolved in DCM (5 ml) and THF (1 ml). 1,3-Dicyclohexylcarbodiimide (0.718 mmol, 0.148 g) was added and the resulting mixture was stirred at RT. The precipitate formed was filtered and (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile (0.359 mmol, 0.1 g), triethylamine (0.359 mmol, 0.036 g) and dry DCM (5 ml) was added to the filtrate. The filtrate was stirred at RT under nitrogen atmosphere for two days during which more 1,3-dicyclohexylcarbodiimide (0.148 g), triethylamine (0.050 ml) and 5-(bromomethyl)isoxazole-3-carboxylic acid (0.1 g) were added. The reaction mixture was diluted with DCM and washed with NaHCO3. The organic phase was dried, filtered and evaporated. The crude product was purified with flash chromatography. 0.064 g of the title compound was obtained. 1H-NMR (400 MHz, CDCl3): δ 1.25 (d, 3H), 4.00-4.09 (m, 2H), 4.23-4.31 (m, 1H), 4.41-4.48 (m, 1H), 4.53-4.63 (m, 1H), 6.60-6.66 (m, 1H), 6.74-6.78 (m, 1H), 7.48-7.53 (m, 1H), 7.64 (d, 1H), 7.79-7.88 (m, 2H).

Workup

  1. customThe precipitate formed
  2. filtrationwas filtered
  3. additionwere added
  4. washwashed with NaHCO3
  5. customThe organic phase was dried
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified with flash chromatography

Sources & evidence

ORD record
ord-e55e6814e3324d9d99ed28abed8ae0c7
Source dataset
uspto-grants-2014_12
Patent number
US08921378B2

Reaction notes

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