Trifluoroacetic acid → HCID 51001894, compound

HRID 2088427Notes

Reaction equation

HRID 2088427 reaction equation
C(OC([NH:8][C:9]1[S:13][C:12](Br)=[N:11][C:10]=1[C:15]([NH:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][C:23]=1[N:24]1[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30]C(=O)OC(C)(C)C)[CH2:25]1)=[O:16])=O)(C)(C)C.[F:38][C:39]1[C:44]([O:45][CH2:46][CH3:47])=[CH:43][CH:42]=[C:41]([F:48])[C:40]=1B(O)O.C(O)(C(F)(F)F)=O>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].C(#N)C>[NH2:8][C:9]1[S:13][C:12]([C:40]2[C:41]([F:48])=[CH:42][CH:43]=[C:44]([O:45][CH2:46][CH3:47])[C:39]=2[F:38])=[N:11][C:10]=1[C:15]([NH:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][C:23]=1[N:24]1[CH2:29][CH2:28][CH2:27][C@H:26]([NH2:30])[CH2:25]1)=[O:16]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 162178932,6-Difluoro-3-ethoxyphenylboronic acidHCID 69811372HCID 69811372, compound

Product 1

HCID 51001894HCID 51001894, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Procedure

A septum sealed microwave tube was charged with (S)-tert-butyl 1-(3-(5-(tert-butoxycarbonylamino)-2-bromothiazole-4-carboxamido)pyridin-4-yl)piperidin-3-ylcarbamate (50 mg, 0.084 mmol), 2,6-difluoro-3-ethoxyphenyl-boronic acid (169 mg, 0.84 mmol), Pd(dppf)Cl2 (13.6 mg, 0.016 mmol) 1M Na2CO3 (0.6 mL, 14.1 mmol) and acetonitrile (3 mL). The mixture was irradiated for 30 min at 120 C. Upon completion of the reaction, the solvent was distilled off and the crude material was dissolved in CH2Cl2 (5 mL) and transferred to a scintillation vial. TFA (0.77 g, 6.7 mmol) was added and the mixture was stirred at room temperature for 30 min. The solvent was distilled off and the crude product was purified via reverse phase HPLC 40% to 80% MeOH in water with 0.1% NH4OH to afford (S)-5-amino-N-(4-(3-aminopiperidin-1-yl)pyridin-3-yl)-2-(3-ethoxy-2,6-difluorophenyl)thiazole-4-carboxamide as a white solid (4.8 mg, 12%). 1H NMR (400 MHz, DMSO) δ 9.35 (s, 1H), 8.27-8.16 (m, 1H), 7.66 (s, 2H), 7.28 (td, J=9.2, 5.1, 1H), 7.23-7.09 (m, 2H), 4.15 (q, J=7.0, 2H), 3.06 (dd, J=41.9, 10.8, 5H), 2.65 (dd, J=15.7, 5.1, 1H), 1.89 (d, J=10.1, 1H), 1.82-1.67 (m, 2H), 1.36 (t, J=7.0, 3H). ESIMS m/z=475.1 (M+1).

Workup

  1. customA septum sealed microwave tube
  2. customThe mixture was irradiated for 30 min at 120 C
  3. customUpon completion of the reaction
  4. distillationthe solvent was distilled off
  5. dissolutionthe crude material was dissolved in CH2Cl2 (5 mL)
  6. distillationThe solvent was distilled off
  7. customthe crude product was purified via reverse phase HPLC 40% to 80% MeOH in water with 0.1% NH4OH

Sources & evidence

ORD record
ord-384c656dcda547cc80277fa31b984f9f
Source dataset
uspto-grants-2013_05
Patent number
US08435976B2

Reaction notes

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