Methyl (S)-2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-(tert-butoxy)acetate → HCID 86700446, compound

HRID 879635Notes

Reaction equation

HRID 879635 reaction equation
Br[C:2]1[S:3][C:4]([N:7]2[CH2:12][CH2:11][N:10]([CH:13]([CH3:15])[CH3:14])[CH2:9][CH2:8]2)=[CH:5][N:6]=1.Br[C:17]1[S:18][C:19]2[C:25]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)=[C:24]([C@H:33]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])[C:34]([O:36][CH3:37])=[O:35])[C:23]([CH3:43])=[CH:22][C:20]=2[N:21]=1>C1(C)C=CC=CC=1.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.[Cu]I>[C:39]([O:38][C@@H:33]([C:24]1[C:23]([CH3:43])=[CH:22][C:20]2[N:21]=[C:17]([C:2]3[S:3][C:4]([N:7]4[CH2:12][CH2:11][N:10]([CH:13]([CH3:15])[CH3:14])[CH2:9][CH2:8]4)=[CH:5][N:6]=3)[S:18][C:19]=2[C:25]=1[C:26]1[CH:27]=[CH:28][C:29]([Cl:32])=[CH:30][CH:31]=1)[C:34]([O:36][CH3:37])=[O:35])([CH3:42])([CH3:40])[CH3:41]

Participants

6

Reactant 2

HCID 86699809Methyl (S)-2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-(tert-butoxy)acetateHCID 86700445HCID 86700445, compound

Product 1

HCID 86700446HCID 86700446, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
110 °C

Procedure

A 5 mL microwave reaction tube was charged with 2-bromo-5-(4-isopropylpiperazin-1-yl)thiazole (12 mg, 0.041 mmol), Pd(PPh3)4 (7 mg, 15 mol %), CuI (4 mg, 30 mol %) and (SnBu3)2 (48 mg, 2 eq.) and toluene (0.5 mL). The reaction was heated to 110° C. in oil bath. (S)-methyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (20 mg, 1.1 eq.) in toluene (4 mL) was added slowly (over 1.5 hours). The reaction was heated at 110° C. in oil bath for 2 hours. The reaction crude was partitioned between ethyl acetate and brine. The organic layer were concentrated and purified by reverse phase column chromatography (5-100% ACN/H2O+0.1% TFA) to give desired product. LCMS-ESI+: calc'd for C31H38ClN4O3S2: 613.2 (M+H+); Found: 613.2 (M+H+).

Workup

  1. temperatureThe reaction was heated at 110° C. in oil bath for 2 hours
  2. customThe reaction crude
  3. customwas partitioned between ethyl acetate and brine
  4. concentrationThe organic layer were concentrated
  5. custompurified by reverse phase column chromatography (5-100% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-3a51caae15a84aabaeb7780344a21b50
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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