Cesium carbonate → HCID 117843369, compound

HRID 2209068Notes

Reaction equation

HRID 2209068 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][C@@H:9]([C@H:11]2[CH2:15][NH:14][C:13](=[O:16])[CH2:12]2)[CH3:10])[C:5]2[N:17]([CH3:20])[CH:18]=[N:19][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:29]2[C:34]3[N:35]=[CH:36][S:37][C:33]=3[CH:32]=[CH:31][CH:30]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.CCOC(C)=O.O>[S:37]1[C:33]2[CH:32]=[CH:31][CH:30]=[C:29]([C:2]3[N:7]=[C:6]([O:8][C@@H:9]([C@H:11]4[CH2:15][NH:14][C:13](=[O:16])[CH2:12]4)[CH3:10])[C:5]4[N:17]([CH3:20])[CH:18]=[N:19][C:4]=4[CH:3]=3)[C:34]=2[N:35]=[CH:36]1

Participants

7

Reactant 3

HCID 10796Cesium carbonate2×HCID 666979304-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzothiazole2×HCID 117843294(R)-4-((R)-1-((6-chloro-3-methyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one

Product 1

HCID 117843369HCID 117843369, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Intermediate 2.06 (30.3 mg, 0.103 mmol), Pd-PEPPSI-IPr precatalyst (7.1 mg, 0.010 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole (34 mg, 0.13 mmol), and Cs2CO3 (102 mg, 0.313 mmol) were taken up in DME (1.15 mL) under Ar. Water (0.57 mL) was added and the resulting mixture was heated to 100° C. After 2.5 h, additional Pd-PEPPSI-IPr precatalyst (7.4 mg, 0.011 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole (34 mg, 0.13 mmol), and Cs2CO3 (100 mg, 0.31 mmol) were added, and the mixture was stirred for an additional 16 h. The reaction mixture was diluted with EtOAc (20 mL) and water (20 mL) and the phases were separated. The aqueous phase was extracted with EtOAc and the combine organic phase was dried over Na2SO4, filtered, and concentrated to afford a crude residue that was purified by silica gel chromatography to provide (R)-4-((R)-1-(6-(benzo[d]thiazol-4-yl)-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 3.22. LCMS-ESI+ (m/z): [M+H]+ calcd for C20H20N5O2S: 394.1; found 394.2. 1H NMR (400 MHz, Chloroform-d) δ 9.07 (s, 1H), 8.68 (s, 1H), 8.20 (dd, J=7.6, 1.2 Hz, 1H), 7.96 (dd, J=8.0, 1.2 Hz, 1H), 7.88 (s, 1H), 7.59-7.49 (m, 1H), 5.84-5.73 (m, 2H), 4.04 (s, 3H), 3.63-3.53 (m, 1H), 3.41 (dd, J=9.7, 6.1 Hz, 1H), 3.02-2.86 (m, 1H), 2.58-2.52 (m, 2H), 1.51 (d, J=6.2 Hz, 3H).

Workup

  1. customthe phases were separated
  2. extractionThe aqueous phase was extracted with EtOAc
  3. dry with materialthe combine organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford a crude residue that
  7. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-5a9e27c480e1475eb953566f18ab137b
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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