Hydrochloric Acid → 5-(1-Piperidin-4-yl-1H-pyrazol-4-yl)-3-(4-trifluoromethylbenzothiazol-2-yl)-pyridin-2-ylamine

HRID 1926393Notes

Reaction equation

HRID 1926393 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:34])=[C:23](B4OC(C)(C)C(C)(C)O4)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl[C:36]1[S:37][C:38]2[CH:44]=[CH:43][CH:42]=[C:41]([C:45]([F:48])([F:47])[F:46])[C:39]=2[N:40]=1.C(=O)([O-])[O-].[K+].[K+].Cl>COCCOC.O.C(Cl)Cl.C(OCC)C.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>[NH:8]1[CH2:9][CH2:10][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:24]=[C:23]([C:36]4[S:37][C:38]5[CH:44]=[CH:43][CH:42]=[C:41]([C:45]([F:48])([F:47])[F:46])[C:39]=5[N:40]=4)[C:22]([NH2:34])=[N:21][CH:20]=3)[CH:16]=[N:15]2)[CH2:12][CH2:13]1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 247289502-Chloro-4-(trifluoromethyl)-1,3-benzothiazoleHCID 534879604-[4-[6-Amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-3-yl]pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 675208855-(1-Piperidin-4-yl-1H-pyrazol-4-yl)-3-(4-trifluoromethylbenzothiazol-2-yl)-pyridin-2-ylamine

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-{4-[6-amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (BB8) (75 mg, 0.16 mmol), 2-chloro-4-trifluoromethyl-1,3-benzothiazole (46 mg, 0.19 mmol), potassium carbonate (66 mg, 0.48 mmol), Pd(PPh3)4 (18 mg, 0.016 mmol) in DME (3 mL) and H2O (1 mL) was evacuated and refilled with N2 (3×), then it was heated at 100° C. for 30 min in the microwave reactor. The mixture was diluted with EtOAc (30 mL), washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (Hex.:EtOAc=30:70→15:85) to give a yellow solid. This material was dissolved in DCM (2 mL) and treated with 1M HCl in diethyl ether (3 mL). The resulting mixture was stirred at room temperature overnight. The title compound was collected by filtration as a yellow solid and washed with DCM. MS (ES+): m/z=445.10 [MH+].

Workup

  1. customwas evacuated
  2. additionrefilled with N2 (3×)
  3. additionThe mixture was diluted with EtOAc (30 mL)
  4. washwashed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography (Hex.:EtOAc=30:70→15:85)
  9. customto give a yellow solid
  10. filtrationThe title compound was collected by filtration as a yellow solid
  11. washwashed with DCM

Sources & evidence

ORD record
ord-238446c660f14fcda49e231fc9d64b1e
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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