Potassium Carbonate → 4-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)benzoic acid

HRID 2067914Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[F:18][CH:19]([F:36])[O:20][C:21]1[CH:26]=[CH:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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>[F:18][CH:19]([F:36])[O:20][C:21]1[CH:26]=[CH:25][C:24]([C:2]2[CH:3]=[N:4][C:5]([NH:8][C:9]3[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=3)=[N:6][CH:7]=2)=[CH:23][CH:22]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To 4-(5-bromopyrimidin-2-ylamino)benzoic acid 53 (0.25 mmol) in 1,4-dioxane (2.0 mL) is added 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 7 (0.28 mmol), 1.8M K2CO3 (0.5 mmol) and Pd(PPh3)4 (0.017 mmol). The reaction is evacuated and backfilled with nitrogen twice then heated at 90° C. for 8 h. The reaction mixture is diluted with water (10 mL) neutralized with 2M HCl and extracted with DCM (3×20 mL). Purification by preparative HPLC (ACN gradient 20-70%) affords 4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)benzoic acid 54 as white solid. MS (m/z) (M+1)+: 358.2.

Workup

customThe reaction is evacuated
additionThe reaction mixture is diluted with water (10 mL)
extractionextracted with DCM (3×20 mL)
customPurification by preparative HPLC (ACN gradient 20-70%)

Sources & evidence

ORD record: ord-b13a68f0d08544788e0f24f589e7f417
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293757B2

Reaction notes

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