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

HRID 2067888Notes

Reaction equation

HRID 2067888 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:26]=[CH:25][C:12]([O:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][CH:19]([C:22]([O-:24])=[O:23])[CH2:18][CH2:17]3)=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[Na+].[F:28][CH:29]([F:46])[O:30][C:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=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:28][CH:29]([F:46])[O:30][C:31]1[CH:36]=[CH:35][C:34]([C:2]2[CH:3]=[N:4][C:5]([NH:8][C:9]3[CH:26]=[CH:25][C:12]([O:13][CH2:14][CH2:15][N:16]4[CH2:21][CH2:20][CH:19]([C:22]([OH:24])=[O:23])[CH2:18][CH2:17]4)=[CH:11][CH:10]=3)=[N:6][CH:7]=2)=[CH:33][CH:32]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 220323032-(4-(Difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 68729241Sodium 1-(2-(4-(5-bromopyrimidin-2-ylamino)phenoxy)ethyl)piperidine-4-carboxylate

Product 1

HCID 251956131-(2-(4-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenoxy)ethyl)piperidine-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of sodium 1-(2-(4-(5-bromopyrimidin-2-ylamino)phenoxy)ethyl)piperidine-4-carboxylate 13 (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 at 150° C. for 10 min. Purification by prep-HPLC (ACN gradient 10-70%) affords 1-(2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenoxy)ethyl)piperidine-4-carboxylic acid A3. 1H NMR (400 MHz, d6-DMSO) δ 9.68 (s, 1H), 8.78 (s, 2H), 7.76 (d, J=8.8 Hz, 2H), 7.71 (d, J=9.2 Hz, 2H), 7.28 (t, J=74.0 Hz, 1H), 7.27 (d, J=8.4 Hz, 2H), 6.98 (d, J=8.8 Hz, 1H), 4.28 (t, J=4.8 Hz, 2H), 3.51 (m, 2H), 3.23 (m, 4H), 1.24 (t, J=7.2, 6H). MS (m/z) (M+1)+: 485.2.

Workup

  1. customThe reaction is evacuated
  2. customPurification by prep-HPLC (ACN gradient 10-70%)

Sources & evidence

ORD record
ord-06d13fc7eca048df815d3b52017a57e0
Source dataset
uspto-grants-2012_10
Patent number
US08293757B2

Reaction notes

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