Hydrochloric Acid → HCID 178422166, compound

HRID 2095739Notes

Reaction equation

HRID 2095739 reaction equation
C(OC([N:8]1[C:12]2=[N:13][CH:14]=[C:15](Br)[CH:16]=[C:11]2[C:10]([CH:18]([C:20]2[C:25]([Cl:26])=[CH:24][CH:23]=[C:22]([F:27])[C:21]=2[OH:28])[CH3:19])=[CH:9]1)=O)(C)(C)C.[Si]([O:36][C@H:37]1[CH2:42][CH2:41][C@H:40]([N:43]2[C:47]([CH3:48])=[C:46](B3OC(C)(C)C(C)(C)O3)[CH:45]=[N:44]2)[CH2:39][CH2:38]1)(C(C)(C)C)(C)C.C(=O)([O-])[O-].[K+].[K+].O.Cl>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.O1CCOCC1>[Cl:26][C:25]1[C:20]([CH:18]([C:10]2[C:11]3[C:12](=[N:13][CH:14]=[C:15]([C:46]4[CH:45]=[N:44][N:43]([C@H:40]5[CH2:41][CH2:42][C@H:37]([OH:36])[CH2:38][CH2:39]5)[C:47]=4[CH3:48])[CH:16]=3)[NH:8][CH:9]=2)[CH3:19])=[C:21]([OH:28])[C:22]([F:27])=[CH:23][CH:24]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 962Water2×HCID 11430Potassium CarbonateHCID 67004033HCID 67004033, compoundHCID 178421688HCID 178421688, compound

Product 1

HCID 178422166HCID 178422166, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5-Bromo-3-[1-(6-chloro-3-fluoro-2-hydroxyphenyl)ethyl]pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (100.00 mg, 0.21289 mmol), 1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (134 mg, 0.319 mmol), Pd(PPh3)4 (12.3 mg, 0.0106 mmol), potassium carbonate (147.1 mg, 1.064 mmol) and 4:1 Dioxane:water (4:1,1,4-Dioxane:H2O, 8 mL, 80 mmol) was heated in a microwave reactor at 100° C. for 30 min. Reaction mixture was cooled to rt, 12 M HCl in H2O (0.8 mL, 10 mmol) was added, and the solution was heated at 40° C. for 2 h. Purification by Teledyne/ISCO eluting with 0-15% MeOH in DCM afforded the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.37-1.59 (m, 2H), 1.84 (d, J=7.3 Hz, 3H), 1.89-2.14 (m, 6H), 2.16-2.27 (m, 3H), 3.68 (ddd, J=10.9, 6.8, 4.3 Hz, 1H), 4.08-4.26 (m, 1H), 5.09 (br. s., 1H), 6.76-6.88 (m, 1H), 6.90-7.00 (m, 1H), 7.37 (d, J=1.3 Hz, 1H), 7.44-7.56 (m, 2H), 8.09 (d, J=2.0 Hz, 1H).

Workup

  1. customReaction mixture
  2. temperaturethe solution was heated at 40° C. for 2 h
  3. customPurification by Teledyne/ISCO
  4. washeluting with 0-15% MeOH in DCM

Sources & evidence

ORD record
ord-69ec995246c54fa3a907e79419846d0d
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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