Hydrochloric Acid → 2-(1-(2-Fluoro-4-(6-(3-(3-(trifluoromethyl)phenyl)ureido)pyridin-3-yl)phenyl)cyclobutoxy)acetic acid

HRID 1397508Notes

Reaction equation

HRID 1397508 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)=[O:17])=[N:13][CH:14]=2)O1.Br[C:31]1[CH:36]=[CH:35][C:34]([C:37]2([O:41][CH2:42][C:43]([OH:45])=[O:44])[CH2:40][CH2:39][CH2:38]2)=[C:33]([F:46])[CH:32]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].O.C(O)C.CN(C)C(=O)C>[F:46][C:33]1[CH:32]=[C:31]([C:9]2[CH:14]=[N:13][C:12]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:26])([F:27])[F:28])[CH:20]=3)=[O:17])=[CH:11][CH:10]=2)[CH:36]=[CH:35][C:34]=1[C:37]1([O:41][CH2:42][C:43]([OH:45])=[O:44])[CH2:40][CH2:39][CH2:38]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 592321581-(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)-3-(3-(trifluoromethyl)phenyl)ureaHCID 687205752-(1-(4-Bromo-2-fluorophenyl)cyclobutoxy)acetic acid

Product 1

HCID 251062362-(1-(2-Fluoro-4-(6-(3-(3-(trifluoromethyl)phenyl)ureido)pyridin-3-yl)phenyl)cyclobutoxy)acetic acid

Reagents, catalysts & solvents 4

HCID 178454861HCID 178454861, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

A 25 mL vial was charged with the product from Example 60C (459 mg, 1.128 mmol), the product from Example 60B (342 mg, 1.128 mmol), dibasic potassium phosphate (590 mg, 3.38 mmol), and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium (II) dichloride (7.38 mg, 0.011 mmol), N,N-dimethylacetamide (4 mL), ethanol (4.00 ml) and water (2 mL). The suspension was stirred and heated to 90° C., whereupon the reaction became homogenous. After heating at 90° C. for 1 hour; the reaction was cooled to room temperature. The resulting suspension was poured into water (200 mL). The mixture was acidified to pH 1 with 1 M HCl. The solid was filtered, washed with water, and air-dried to give the title product. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.62-1.71 (m, 1 H), 1.96-2.07 (m, 1 H), 2.39-2.49 (m, 4 H), 3.69 (s, 2 H), 7.38 (d, J=7.12Hz, 1 H), 7.47-7.61 (m, 4 H), 7.65-7.71 (m, 2 H), 8.07 (s, 1 H), 8.17 (dd, J=2.7 and 8.8 Hz, 1 H), 8.71 (d, J=2.7 Hz, 1 H), 9.68 (s, 1 H), 10.65 (s, 1 H), 12.5 (br s, 1 H). MS (ESI) m/z 504 [M+H]+.

Workup

  1. temperatureAfter heating at 90° C. for 1 hour
  2. temperaturethe reaction was cooled to room temperature
  3. filtrationThe solid was filtered
  4. washwashed with water
  5. customair-dried

Sources & evidence

ORD record
ord-2d4ed0e6d2fb40bf82b2f6daf105acb1
Source dataset
uspto-grants-2014_12
Patent number
US08901152B2

Reaction notes

Loading…