Sodium Carbonate → 2-(4-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid

HRID 2067876Notes

Reaction equation

HRID 2067876 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH:15]([CH2:19][OH:20])[C:16]([OH:18])=[O:17])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[F:21][CH:22]([F:39])[O:23][C:24]1[CH:29]=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:25]=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:21][CH:22]([F:39])[O:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[CH:3]=[N:4][C:5]([NH:8][C:9]3[CH:14]=[CH:13][C:12]([CH:15]([CH2:19][OH:20])[C:16]([OH:18])=[O:17])=[CH:11][CH:10]=3)=[N:6][CH:7]=2)=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 220323032-(4-(Difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 687270502-(4-(5-Bromopyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid

Product 1

HCID 585422202-(4-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 2-(4-(5-bromopyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid 25 (0.5 mmol) in 1,4-dioxane (2 mL) is added 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 7 (0.5 mmol), Na2CO3 (1.5 mmol of a 3.0 M aq. solution) and Pd(PPh3)4 (0.025 mmol). The reaction is evacuated and backfilled with nitrogen twice then heated at 150° C. for 10 min. The reaction mixture is diluted with water (10 mL). The aqueous layer is washed with DCM (2×50 mL) and acidified to pH 5 using aqueous HCl (1 N). The resulting mixture is extracted with DCM (2×50 mL). The organic layer is separated, dried over Na2SO4 and concentrated to yield a crude 2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid 26 which is used without further purification. 1H NMR (400 MHz, d6-DMSO) δ 9.65 (s, 1H), 8.79 (s, 2H), 7.76 (d, J=8.8 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H), 7.30 (s, 1H), 7.27 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.4 Hz, 2H), 3.60-3.70 (m, 2H), 3.50-3.58 (m, 2H), 3.20-3.26 (m, 2H). MS (m/z) (M+1)+: 402.1.

Workup

  1. customThe reaction is evacuated
  2. additionThe reaction mixture is diluted with water (10 mL)
  3. washThe aqueous layer is washed with DCM (2×50 mL)
  4. extractionThe resulting mixture is extracted with DCM (2×50 mL)
  5. customThe organic layer is separated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-8999eb96258548ef8b57ec98e35a6c91
Source dataset
uspto-grants-2012_10
Patent number
US08293757B2

Reaction notes

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