Hydrochloric Acid → [4-(3'-Chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-phenyl]-thiazol-2-yl-amine

HRID 1632031Notes

Reaction equation

HRID 1632031 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[C:10]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=3)[C:9]=2[F:24])[CH:5]=[CH:6][CH:7]=1.Br[C:26]1[S:27][CH:28]=[CH:29][N:30]=1.Cl.C(=O)([O-])[O-].[K+].[K+]>O.C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[C:10]([CH2:16][C:17]3[CH:18]=[CH:19][C:20]([NH:23][C:26]4[S:27][CH:28]=[CH:29][N:30]=4)=[CH:21][CH:22]=3)[C:9]=2[F:24])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 764302-BromothiazoleHCID 580200234-(3'-Chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-phenylamine

Product 1

HCID 58020373[4-(3'-Chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-phenyl]-thiazol-2-yl-amineYield 45%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

(P-443): In an 8 mL vial equipped with a stir bar was placed 4-(3′-chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-phenylamine (I-35) synthesized above (100 mg, 0.293 mmol), 2-bromothiazole (52.1 μL, 0.585 mmol), 10% aqueous ethanol (1.5 mL) and concentrated hydrochloric acid (48.8 μL, 0.585 mmol). The mixture was heated to 90° C. for 18 hours and then cooled to room temperature. After water (30 mL) and 5% aqueous potassium carbonate (30 mL) were added, the aqueous portion was extracted with ethyl acetate (2×35 mL) and the organic portions were combined, washed brine (30 mL), dried (magnesium sulfate) and concentrated. The crude material was purified by column chromatography utilizing 3% acetone/dichloromethane as the eluent to produce 57 mg of [4-(3′-chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-phenyl]-thiazol-2-yl-amine. (P-443) as white solid in 45% yield. 1H NMR (400 MHz, CDCl3) δ 3.75 (s, 3H), 3.94 (s, 2H), 6.62 (d, J=4 Hz, 1H), 6.70 (dd, J=8, 1 Hz, 1H), 7.10 (t, J=9 Hz, 1H), 7.20-7.22 (m, 2H), 7.26-7.40 (m, 8H) ppm; MS (APCI+): 425.0 (M+1), LC-MS: 89%

Workup

  1. custom(P-443): In an 8 mL vial equipped with a stir bar
  2. temperaturecooled to room temperature
  3. extractionthe aqueous portion was extracted with ethyl acetate (2×35 mL)
  4. washwashed brine (30 mL)
  5. dry with materialdried (magnesium sulfate)
  6. concentrationconcentrated
  7. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-64480119e1d44ff0847c3893bc588812
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

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