Sodium Carbonate → 1-(4-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenethyl)piperidine-4-carboxylic acid

HRID 2067891Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:25]=[CH:24][C:12]([CH2:13][CH2:14][N:15]3[CH2:20][CH2:19][CH:18]([C:21]([OH:23])=[O:22])[CH2:17][CH2:16]3)=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[F:26][CH:27]([F:44])[O:28][C:29]1[CH:34]=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=1.C([O-])([O-])=O.[Na+].[Na+]>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:26][CH:27]([F:44])[O:28][C:29]1[CH:34]=[CH:33][C:32]([C:2]2[CH:3]=[N:4][C:5]([NH:8][C:9]3[CH:25]=[CH:24][C:12]([CH2:13][CH2:14][N:15]4[CH2:20][CH2:19][CH:18]([C:21]([OH:23])=[O:22])[CH2:17][CH2:16]4)=[CH:11][CH:10]=3)=[N:6][CH:7]=2)=[CH:31][CH:30]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of 1-(4-(5-bromopyrimidin-2-ylamino)phenethyl)piperidine-4-carboxylic acid 21 (0.05 mmol) in 1,4-dioxane (1.0 mL) is added 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 7 (0.05 mmol), 3M Na2CO3 (0.15 mmol) and Pd(PPh3)4 (0.0025 mmol). The reaction is evacuated and backfilled with nitrogen twice then heated in a microwave oven at 150° C. for 10 min. Purification by preparative HPLC (ACN gradient 10-70%) affords 1-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenethyl)piperidine-4-carboxylic acid A6. MS (m/z) (M+1)+: 469.2.

Workup

customThe reaction is evacuated
customPurification by preparative HPLC (ACN gradient 10-70%)

Sources & evidence

ORD record: ord-e23a4a8542c14fe8bca45dd1c7449161
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293757B2

Reaction notes

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