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Potassium Carbonate → 5-(1-azetidin-3-yl-1H-pyrazol-4-yl)-3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

HRID 2046929
Notes
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Reaction equation

HRID 2046929 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[CH:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18](B3OC(C)(C)C(C)(C)O3)[CH:19]=2)[NH:14][CH:13]=1)[CH3:11].C(OC([N:37]1[CH2:40][CH:39]([N:41]2[CH:45]=[C:44](I)[CH:43]=[N:42]2)[CH2:38]1)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>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.O>[NH:37]1[CH2:40][CH:39]([N:41]2[CH:45]=[C:44]([C:18]3[CH:19]=[C:20]4[C:12]([CH:10]([C:3]5[C:4]([Cl:9])=[CH:5][CH:6]=[C:7]([F:8])[C:2]=5[Cl:1])[CH3:11])=[CH:13][NH:14][C:15]4=[N:16][CH:17]=3)[CH:43]=[N:42]2)[CH2:38]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 584314473-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridineHCID 58431448tert-butyl 3-(4-iodo-1H-pyrazol-1-yl)azetidine-1-carboxylate

Product 1

HCID 462154755-(1-azetidin-3-yl-1H-pyrazol-4-yl)-3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst
HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (100.0 mg, 0.230 mmol), 3-(4-iodopyrazol-1-yl)-azetidine-1-carboxylic acid tert-butyl ester (88.3 mg, 0.253 mmol), Pd(PPh3)4 (10 mg, 0.01 mmol), potassium carbonate (95.3 mg, 0.689 mmol) and 4:1 dioxane/H2O (8 mL) was heated to 90° C. for 2 h. The organic solvent was removed in vacuo, and the material was transferred to a separatory funnel, extracting with DCM and water. The organic layer was concentrated in vacuo, redissolved in dioxane, and 4M HCl in dioxane (1 mL) was added. The solution was heated to 45° C. for 3 h. The solvents were removed on the corrosive pump, and the material was dry-loaded onto silica gel for column chromatography, eluting with 3-6% (7N NH3 in MeOH)/DCM. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a yellow solid. 1H NMR (400 MHz, CD3OD): δ 1.88 (d, J=7.3 Hz, 3 H), 3.90-3.98 (m, 2 H), 4.08-4.15 (m, 2 H), 5.20-5.34 (m, 2 H), 7.18 (t, J=8.6 Hz, 1 H), 7.36 (d, J=1.3 Hz, 1 H), 7.36-7.48 (m, 2 H), 7.65 (s, 1 H), 7.95 (s, 1 H), 8.32 (d, J=2.0 Hz, 1 H). MS (ES+): m/z 430.10 (100) [MH+]. HPLC: tR=2.25 min (ZQ3, polar—5 min).

Workup

  1. customThe organic solvent was removed in vacuo
  2. customthe material was transferred to a separatory funnel
  3. extractionextracting with DCM and water
  4. concentrationThe organic layer was concentrated in vacuo
  5. dissolutionredissolved in dioxane
  6. addition4M HCl in dioxane (1 mL) was added
  7. temperatureThe solution was heated to 45° C. for 3 h
  8. customThe solvents were removed on the corrosive pump
  9. washeluting with 3-6% (7N NH3 in MeOH)/DCM
  10. additionThe fractions containing the pure product
  11. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-d6b5cf02e8ce40dd8038a1ee9cb0bae9
Source dataset
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08592448B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes