Hydrochloric Acid → HCID 44159051, compound

HRID 1926440Notes

Reaction equation

HRID 1926440 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.I[C:36]1[S:37][C:38]2[CH2:44][CH2:43][CH2:42][CH2:41][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[CH2:44][CH2:43][CH2:42][CH2:41][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 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 esterHCID 67521244HCID 67521244, compound

Product 1

HCID 44159051HCID 44159051, compound

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) (30 mg, 0.064 mmol), 2-iodo-4,5,6,7-tetrahydrobenzothiazole (20 mg, 0.077 mmol), potassium carbonate (26 mg, 0.19 mmol), and Pd(PPh3)4 (7.4 mg, 0.0064 mmol) in DME (1.5 mL) and H2O (0.5 mL) was evacuated and refilled with N2 (3×). It was then 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 anhydrous sodium sulfate, 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 IM HCl in diethyl ether (3 mL). The resulting mixture was stirred at room temperature for 3 h. The title compound was collected by filtration as a yellow solid, washed with DCM, and dried in vacuo. 1H NMR (DMSO-d6, 400 MHz): δ=1.82-1.88 (m, 4H), 2.14-2.23 (m, 4H), 2.81-2.87 (m, 4H), 3.35-3.40 (m, 2H), 4.55 (mc, 1H), 8.09 (s, 1H), 8.44 (d, J=2.0 Hz, 1H), 8.47 (s, 1H), 8.50 (d, J=2.0 Hz, 1H). MS (ES+): m/z=381.17 [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 anhydrous sodium sulfate
  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
  12. customdried in vacuo

Sources & evidence

ORD record
ord-0f73bff4695b46f0acdd1794ff1fb09c
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

Loading…