Binap, (A+-)- → HCID 59326791, compound

HRID 410175Notes

Reaction equation

HRID 410175 reaction equation
Cl[C:2]1[C:7]([N:8]2[CH2:13][CH2:12][CH:11]([O:14][CH3:15])[CH2:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[S:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N:18]=[C:17]1[NH:25][C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:15][O:14][CH:11]1[CH2:12][CH2:13][N:8]([C:7]2[C:2]([O:32][C:29]3[CH:28]=[CH:27][C:26]([NH:25][C:17]4[S:16][C:20]5[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=5[N:18]=4)=[CH:31][CH:30]=3)=[N:3][CH:4]=[CH:5][CH:6]=2)[CH2:9][CH2:10]1

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 593268134-(Benzo[d]thiazol-2-ylamino)phenolHCID 59327226HCID 59327226, compound

Product 1

HCID 59326791HCID 59326791, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

The mixture of 2-chloro-3-(4-methoxypiperidin-1-yl)pyridine (25.0 mg, 0.11 mmol), 4-(benzo[d]thiazol-2-ylamino)phenol (32.1 mg, 0.132 mmol), Pd2(dba)3 (5.05 mg, 5.51 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (5.15 mg, 8.27 μmol) and sodium 2-methylpropan-2-olate (26.5 mg, 0.276 mmol) in toluene (440 μL) was sparged under argon for 5 min. The mixture was heated to 120° C. in a microwave reactor for 10 min. More phenol (32 mg) was added and the reaction mixture was heated at 120° C. in microwave for another 25 min. After cooling to RT, the mixture was filtered through celite and washed with DCM. The crude product was purified by silica gel chromatography (12 g, 0-50% EtOAc-hexane) to give N-(4-(3-(4-methoxypiperidin-1-yl)pyridin-2-yloxy)phenyl)benzo[d]thiazol-2-amine as off-white solid. MS (ESI, pos. ion) m/z: 433.0 (M+1). IC50 (uM) +++++.

Workup

  1. customwas sparged under argon for 5 min
  2. additionMore phenol (32 mg) was added
  3. temperaturethe reaction mixture was heated at 120° C. in microwave for another 25 min
  4. temperatureAfter cooling to RT
  5. filtrationthe mixture was filtered through celite
  6. washwashed with DCM
  7. customThe crude product was purified by silica gel chromatography (12 g, 0-50% EtOAc-hexane)

Sources & evidence

ORD record
ord-2df621000ad84dedb4f7c4df3c9c4a48
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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