Acetic Acid → HCID 86700209, compound

HRID 879403Notes

Reaction equation

HRID 879403 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([N:12]([CH3:14])[CH3:13])=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.C(Cl)Cl.CC(O)=O.CC([O-])=O.[K+].Br[C:28]1[S:29][C:30]2[C:36]([C:37]3[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=3)=[C:35]([C@H:44]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])[C:45]([O:47]CC)=[O:46])[C:34]([CH3:55])=[CH:33][C:31]=2[N:32]=1.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].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.CCO.O1CCOCC1>[C:51]([O:50][C@@H:44]([C:35]1[C:34]([CH3:55])=[CH:33][C:31]2[N:32]=[C:28]([C:2]3[CH:10]=[C:9]4[C:5]([C:6]([N:12]([CH3:14])[CH3:13])=[N:7][N:8]4[CH3:11])=[CH:4][CH:3]=3)[S:29][C:30]=2[C:36]=1[C:37]1[CH:38]=[CH:39][C:40]([Cl:43])=[CH:41][CH:42]=1)[C:45]([OH:47])=[O:46])([CH3:54])([CH3:52])[CH3:53]

Participants

12

Reactant 7

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 517044Potassium AcetateHCID 86700141(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetateHCID 86700210HCID 86700210, compound

Product 1

HCID 86700209HCID 86700209, compound

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with 6-bromo-N,N,1-trimethyl-1H-indazol-3-amine (102 mg, 0.402 mmol), bis-pinacolatodiboron (112 mg, 0.442 mmol), PdCl2(dppf).DCM (33 mg, 40 μmol), glacial AcOH (25 μL, 0.44 mmol), KOAc (130 mg, 1.33 mmol), and dioxane (2.0 mL). The reaction was heated to 100° C. for 30 min. To this reaction was added (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (150 mg, 0.302 mmol), 2 M aq K2CO3 (884 μL), and Pd(PPh3)4 (46 mg, 40 mop. The reaction was heated for another 1 h at 100° C. Finally, EtOH (absolute, 1.7 mL) and 2 M aqueous NaOH (884 μL) were added. The reaction was heated to 100° C. for another 1 h. The reaction was cooled to 23° C., and filtered (0.45 micron teflon syringe filter). The filtrate was purified by reverse phase HPLC, eluting by 5-100% acetonitrile in H2O with 0.1% TFA to give the desired product. LCMS-ESI+: calc'd for C30H31ClN4O3S: 563.2, 565.2 (M+H+); Found: 563.2, 565.2 (M+H+). 1H NMR (400 MHz, CD3OD): δ 8.01 (s, 1H), 7.93 (d, J=8.6 Hz, 1H), 7.84 (s, 1H), 7.69 (dd, J=6.3, 3.2 Hz, 1H), 7.65 (dd, J=8.6, 1.2 Hz, 1H), 7.62-7.56 (m, 3H), 5.26 (s, 1H), 3.90 (s, 3H), 3.12 (s, 6H), 2.61 (d, J=4.8 Hz, 3H), 0.98 (d, J=4.1 Hz, 9H).

Workup

  1. temperatureThe reaction was heated for another 1 h at 100° C
  2. temperatureThe reaction was heated to 100° C. for another 1 h
  3. temperatureThe reaction was cooled to 23° C.
  4. filtrationfiltered
  5. filtration(0.45 micron teflon syringe filter)
  6. customThe filtrate was purified by reverse phase HPLC
  7. washeluting by 5-100% acetonitrile in H2O with 0.1% TFA

Sources & evidence

ORD record
ord-590674f4b98f4c048aed65d2104f93fb
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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