Sodium Carbonate → (4-{4-[2-(3-Fluorophenylamino)-thiazol-4-yl]-phenyl}-cyclohexyl)-acetic acid

HRID 1404228Notes

Reaction equation

HRID 1404228 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=3)[S:11][CH:12]=2)=[CH:4][CH:3]=1.CC(C)(C[C:27](=O)[C:28]1[CH:33]=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][CH:29]=1)C(O)=O.[C:45](=[O:48])([O-])[O-:46].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:20][C:16]1[CH:15]=[C:14]([NH:13][C:10]2[S:11][CH:12]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([CH:31]4[CH2:32][CH2:33][CH:28]([CH2:27][C:45]([OH:46])=[O:48])[CH2:29][CH2:30]4)=[CH:3][CH:4]=3)[N:9]=2)[CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 66615890α,α-Dimethyl-γ-oxo-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenebutanoic acidHCID 86634687HCID 86634687, compound

Product 1

HCID 24937517(4-{4-[2-(3-Fluorophenylamino)-thiazol-4-yl]-phenyl}-cyclohexyl)-acetic acid

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
120 °C

Procedure

To a microwave vial is added [4-(4-bromophenyl)-thiazol-2-yl]-(3-fluorophenyl)-amine (92 mg, 0.26 mmol), 2,2-dimethyl-4-oxo-4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-butyric acid (half of the crude from last step), sodium carbonate (2M solution, 0.526 mL) and resin bound Pd(PPh3)4 (130 mg, 0.013 mmol). The reaction mixture is sparged with nitrogen for 2 min and then heated in a microwave at 120° C. for 20 min. The resin is then filtered off and the filtrate is concentrated. The residue is titrate with ether. The resulting yellow solid is purified by reverse-phase preparative HPLC to give the title compound: 1H NMR (400 MHz, DMSO-D6) δ ppm 1.24 (s, 6 H), 2.49 (d, J=3.54 Hz, 4 H), 3.34 (s, 8 H), 6.73-6.82 (m, 1H), 7.05 (s, 2 H), 7.17 (s, 3 H), 7.33 (s, 2 H), 7.35-7.40 (m, 2 H), 7.50 (s, 1 H), 7.81-7.90 (m, 5 H), 8.04 (dd,J=8.34, 2.53 Hz, 4 H), 10.56 (s, 1 H); (M+H)+=475.0.

Workup

  1. customThe reaction mixture is sparged with nitrogen for 2 min
  2. filtrationThe resin is then filtered off
  3. concentrationthe filtrate is concentrated
  4. customThe resulting yellow solid is purified by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-dd7f7590237c403f9a3d251983474209
Source dataset
uspto-grants-2014_12
Patent number
US08912208B2

Reaction notes

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