Hydrochloric Acid → HCID 58247965, compound

HRID 2371084Notes

Reaction equation

HRID 2371084 reaction equation
[C:1](Cl)(=[O:5])[CH:2]([CH3:4])[CH3:3].Cl.[NH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[C:18]([NH:20][CH:21]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=2)[C:22]([F:25])([F:24])[F:23])=[O:19])=[CH:12][C:11]=1[C:36]([F:39])([F:38])[F:37].CCN(C(C)C)C(C)C>ClCCl>[C:1]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[C:18]([NH:20][CH:21]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:33])([F:34])[F:35])[CH:27]=2)[C:22]([F:23])([F:24])[F:25])=[O:19])=[CH:12][C:11]=1[C:36]([F:37])([F:38])[F:39])(=[O:5])[CH:2]([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 62325Isobutyryl chlorideHCID 81531DiisopropylethylamineHCID 58247998HCID 58247998, compound

Product 1

HCID 58247965HCID 58247965, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

30 mg (1.2 eq, 0.28 mmol) of isobutyryl chloride were dissolved in 1 ml of dichloromethane. To this were added 113 mg (1.0 eq, 0.24 mmol) of the hydrochloride of (2E)-3-[4-(aminomethyl)-3-(trifluoromethyl)phenyl]-N-(2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl)acrylamide from Stage 5 and 93 mg (3 eq) of Hünig's base. The mixture was stirred at room temperature for 16 h then concentrated. The crude product was purified by means of preparative HPLC (Phenomenex Gemini C18 5 μm; 125A; Aqua 50×21.2 mm; gradient: 0-1.5 min 78% water, 20% acetonitrile, 1.5-10.0 min linear gradient to 18% water, 80% acetonitrile, 10.0-14.00 min 18% water, 20% acetonitrile; modifier: 10% NH4HCO3 added at 2 ml/min). This gives 57 mg (44%) of (2E)-3-{4-[(isobutyrylamino)methyl]-3-(trifluoroethyl)phenyl}-N-{2,2,2-trifluoro-1-[3-(trifluoro-methyl)phenyl]ethyl}acrylamide.

Workup

  1. concentrationthen concentrated
  2. customThe crude product was purified by means of preparative HPLC (Phenomenex Gemini C18 5 μm; 125A; Aqua 50×21.2 mm; gradient: 0-1.5 min 78% water, 20% acetonitrile, 1.5-10.0 min linear gradient to 18% water, 80% acetonitrile, 10.0-14.00 min 18% water, 20% acetonitrile; modifier: 10% NH4HCO3 added at 2 ml/min)

Sources & evidence

ORD record
ord-4340b682b55b46009634b4004ab6ce3e
Source dataset
uspto-grants-2014_04
Patent number
US08710242B2

Reaction notes

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