Trifluoroacetic acid → HCID 178451145, compound

HRID 2207377Notes

Reaction equation

HRID 2207377 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([C:8]([C@H:11]2[CH2:16][CH2:15][C@H:14]([C:17]([O:19][CH2:20][CH2:21][CH2:22][CH3:23])=[O:18])[CH2:13][CH2:12]2)([OH:10])[CH3:9])=[N:6][CH:7]=1.[CH:24]1([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34]3[CH:39]=[C:38](B4OC(C)(C)C(C)(C)O4)[CH:37]=[C:36]([CH3:49])[CH:35]=3)[N:28]=2)[CH2:26][CH2:25]1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Na+].[Na+].C(O)(C(F)(F)F)=O>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].O1CCOCC1>[CH:24]1([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34]3[CH:39]=[C:38]([C:2]4[CH:3]=[CH:4][C:5]([C:8]([C@H:11]5[CH2:16][CH2:15][C@H:14]([C:17]([O:19][CH2:20][CH2:21][CH2:22][CH3:23])=[O:18])[CH2:13][CH2:12]5)([OH:10])[CH3:9])=[N:6][CH:7]=4)[CH:37]=[C:36]([CH3:49])[CH:35]=3)[N:28]=2)[CH2:26][CH2:25]1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 25112535BrettphosHCID 672563904-cyclopropyl-N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amineHCID 178451146HCID 178451146, compound

Product 1

HCID 178451145HCID 178451145, compound

Reagents, catalysts & solvents 2

HCID 25112666BrettPhos PalladacycleCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of trans-butyl 4-(1-(5-chloropyridin-2-yl)-1-hydroxyethyl)cyclohexanecarboxylate (110 mg, 0.324 mmol), 4-cyclopropyl-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amine (114 mg, 0.324 mmol), BrettPhos Precatalyst (13.0 mg, 0.016 mmol), BrettPhos (18.0 mg, 0.034 mmol) and sodium carbonate (330 μl, 0.660 mmol) in dioxane (1618 μl) was heated to 100° C. for 2 hours. The reaction mixture was cooled to room temperature and TFA (0.5 mL) was added. The reaction mixture was purified directly by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water+0.1% TFA (45-80%). The major peak was collected and lyophilized to give trans-butyl 4-(1-(5-(3-(4-cyclopropylpyrimidin-2-ylamino)-5-methylphenyl)pyridin-2-yl)-1-hydroxyethyl)cyclohexanecarboxylate as a colorless solid. MS ESI calc'd for C32H41N4O3 [M+H]+ 529. found 529.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe reaction mixture was purified directly by preparative HPLC Reverse phase (C-18)
  3. washeluting with Acetonitrile/Water+0.1% TFA (45-80%)
  4. customThe major peak was collected

Sources & evidence

ORD record
ord-89d2ccd224fa49caa9715637f8cec75f
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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