Hydrochloric Acid → HCID 67521238, compound

HRID 1926377Notes

Reaction equation

HRID 1926377 reaction equation
C(OC(N1CCCCC1[N:14]1[CH:18]=[C:17]([C:19]2[CH:20]=[N:21][C:22]([NH2:35])=[C:23]([C:25]3[S:26][C:27]4[C:33](Br)=[CH:32][CH:31]=[CH:30][C:28]=4[N:29]=3)[CH:24]=2)[CH:16]=[N:15]1)=O)(C)(C)C.[NH:36]1[CH:40]=[C:39](B(O)O)[CH:38]=[N:37]1.C(=O)([O-])[O-].[K+].[K+].[ClH:50]>O1CCOCC1.O.C(Cl)Cl.CCOCC.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]>[ClH:50].[ClH:50].[NH:21]1[CH2:22][CH2:23][CH:24]([N:14]2[CH:18]=[C:17]([C:19]3[CH:24]=[C:23]([C:25]4[S:26][C:27]5[C:33]([C:39]6[CH:38]=[N:37][NH:36][CH:40]=6)=[CH:32][CH:31]=[CH:30][C:28]=5[N:29]=4)[C:22]([NH2:35])=[N:21][CH:20]=3)[CH:16]=[N:15]2)[CH2:19][CH2:20]1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 177502781H-Pyrazole-4-boronic acidHCID 67520904HCID 67520904, compound

Product 1

HCID 67521238HCID 67521238, compound

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-[6-amino-5-(7-bromobenzothiazol-2-yl)-pyridin-3-yl]-pyrazol-1-ylpiperidine-1-carboxylic acid tert-butyl ester (30 mg, 0.050 mmol), 4-pyrazoleboronic acid (12 mg, 0.11 mmol), potassium carbonate (20 mg, 0.20 mmol) and Pd(dppf)Cl2 (2 mg, 0.01 mmol) in 1,4-dioxane (1.2 mL) and H2O (0.4 mL) was left to stir at 100° C. for 30 min in the microwave reactor. Then, the mixture was passed through PL-Thiol MP SPE resin and the filtrate was concentrated in vacuo. The resulting oil was partitioned between DCM and H2O (3×). The combined organic extracts were treated with brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The Boc-protected intermediate was isolated via prep TLC (5% MeOH in DCM), MS (ES+): m/z=543 [MH+]. The resulting solid was taken up in DCM (1.0 mL) and 1M HCl in ether (1.0 mL) was added. The mixture was left to stir at rt for 1 h. The resulting precipitate was collected by vacuum filtration and washed with DCM, which afforded the title compound as a yellow solid. 1H NMR (400 MHz, CD3OD): δ=2.30-2.44 (m, 4H), 3.21-3.29 (m, 2H), 3.56-3.67 (m, 2H), 4.59-4.71 (m, 1H), 7.68 (t, J=7.8 Hz, 1H), 7.79 (d, J=6.8 Hz, 1H), 8.07-8.12 (m, 2H), 8.27 (s, 2H), 8.37 (d, J=2.0 Hz, 1H), 8.42 (s, 1H), 8.85 (d, J=1.8 Hz, 1H), MS (ES+): m/z=443.14 (100) [MH+]. HPLC: tR=1.77 min (ZQ3, nonpolar—5 min).

Workup

  1. concentrationthe filtrate was concentrated in vacuo
  2. customThe resulting oil was partitioned between DCM and H2O (3×)
  3. additionThe combined organic extracts were treated with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customwas isolated via prep TLC (5% MeOH in DCM), MS (ES+)
  7. waitThe mixture was left
  8. stirringto stir at rt for 1 h
  9. filtrationThe resulting precipitate was collected by vacuum filtration
  10. washwashed with DCM, which

Sources & evidence

ORD record
ord-60d33176dbe54b0ba64c7467da69f998
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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