Potassium Phosphate, Tribasic → HCID 66905561, compound

HRID 2040962Notes

Reaction equation

HRID 2040962 reaction equation
Cl[C:2]1[CH:16]=[CH:15][C:5]2[N:6]=[C:7]([N:9]3[CH2:13][CH2:12][C@H:11]([OH:14])[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[C:17]([C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1)#[N:18].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(O)(C)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[OH:14][C@H:11]1[CH2:12][CH2:13][N:9]([C:7]2[S:8][C:4]3[CH:3]=[C:2]([C:22]4[CH:23]=[CH:24][C:19]([C:17]#[N:18])=[CH:20][CH:21]=4)[CH:16]=[CH:15][C:5]=3[N:6]=2)[CH2:10]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343264-Cyanophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 66905520HCID 66905520, compound

Product 1

HCID 66905561HCID 66905561, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 21881414Toluene isopropyl alcoholSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of (S)-1-(6-chlorobenzo[d]thiazol-2-yl)pyrrolidin-3-ol (Reference Example 13a, 0.2547 g, 1.0 mmol), 4-cyanophenylboronic acid (CAS #126747-14-6, 0.2204 g, 1.5 mmol), palladium (II) acetate (2.2 mg, 0.01 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (CAS #657408-07-6, 0.0102 g, 0.025 mmol), and potassium phosphate (0.4246 g, 2.0 mmol) in toluene/isopropanol (2 mL/2 mL) was heated under microwave irradiation at 150° C. for 10 minutes. The reaction mixture was then cooled to room temperature and concentrated under reduced pressure. This residue was partitioned between ethyl acetate and saturated aqueous sodium carbonate. The organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography (80:20 to 60:40 hexane/isopropanol). Fractions containing product were combined and concentrated under reduced pressure to provide (S)-4-(2-(3-hydroxypyrrolidin-1-yl)benzo[d]thiazol-6-yl)benzonitrile. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.91-2.02 (m, 1H), 2.06-2.19 (m, 1H), 3.38-3.46 (m, 1H), 3.56-3.68 (m, 3H), 4.41-4.48 (m, 1H), 5.14 (d, J=4 Hz, 1H), 7.54 (d, J=8 Hz, 1H), 7.68 (dd, J=2, 8 Hz, 1H), 7.89 (s, 1H), 8.23 (d, J=2 Hz, 1H); MS (DCI/NH3) m/z 322 (M+H)+.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. customThis residue was partitioned between ethyl acetate and saturated aqueous sodium carbonate
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by silica gel chromatography (80:20 to 60:40 hexane/isopropanol)
  8. additionFractions containing product
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3e436b3cc8b34f40864d6d78832b6c22
Source dataset
uspto-grants-2013_11
Patent number
US08580968B2

Reaction notes

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