1-Hydroxybenzotriazole → HCID 71493649, compound

HRID 1486969Notes

Reaction equation

HRID 1486969 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([OH:22])=O)[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CCN=C=NCCCN(C)C.Cl.Cl.[F:38][C:39]1([F:45])[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl>[F:11][C:9]([F:10])([F:12])[C:7]1[CH:6]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([N:42]3[CH2:43][CH2:44][C:39]([F:45])([F:38])[CH2:40][CH2:41]3)=[O:22])[N:14]=2)[CH:4]=[C:3]([C:2]([F:1])([F:23])[F:24])[CH:8]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27583514,4-Difluoropiperidine hydrochlorideHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

Product 1

HCID 71493649HCID 71493649, compoundYield 13.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A cold (0° C.) solution of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (4) (0.500 g, 1.0 eq.) in CH2Cl2 (20 mL) was treated sequentially with EDC HCl (0.409 g, 1.5 eq.), 4,4-difluoropiperidine hydrochloride (0.269 g, 1.2), DIPEA (0.220 g, 1.2 eq) and HOBT (0.261 g, 1.2 eq.). The clear reaction mixture was stirred at 0° C. for 1.5-2 h then quenched with 50 mL ice-water slurry. The aqueous layer was extracted with CH2Cl2 (2×25 mL) and the combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford 0.60 g of crude compound. Purification by preparative TLC (eluting with MeOH/CH2Cl2) afforded 0.090 g compound which was further triturated using ether: petroleum ether to remove aliphatic impurity affording 0.06 g pure compound. Yield: 9.28%.

Workup

  1. customthen quenched with 50 mL ice-water slurry
  2. extractionThe aqueous layer was extracted with CH2Cl2 (2×25 mL)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto afford 0.60 g of crude compound
  7. customPurification
  8. washby preparative TLC (eluting with MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-29e3145ab5614dfd82400d0f069a12df
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

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