Cesium carbonate → HCID 49838784, compound

HRID 713681Notes

Reaction equation

HRID 713681 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]2[N:6]=[C:7]([C@H:9]3[CH2:12][C@H:11]([N:13]4[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]4)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[OH:21][C@H:22]1[CH2:26][CH2:25][NH:24][C:23]1=[O:27].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+].[Al]>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]>[OH:21][C@H:22]1[CH2:26][CH2:25][N:24]([C:2]2[CH:20]=[CH:19][C:5]3[N:6]=[C:7]([CH:9]4[CH2:12][CH:11]([N:13]5[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]5)[CH2:10]4)[S:8][C:4]=3[CH:3]=2)[C:23]1=[O:27]

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 5359268AluminumHCID 11029774(3S)-3-hydroxypyrrolidin-2-oneHCID 178419317HCID 178419317, compound

Product 1

HCID 49838784HCID 49838784, compoundYield 40.4%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
150 °C

Procedure

To a microwave vial equipped with magnetic stir bar, 50 mg (0.14 mmol) of 6-bromo-2-[trans-3-(1-piperidinyl)cyclobutyl]benzothiazole (prepared as described in Cowart, et al. Benzothiazole cyclobutylamine derivatives, US Patent Publication No. 2007/0066588(A1)) was added, followed by (S)-3-hydroxypyrrolidin-2-one (50 mg, 0.50 mmol), Pd2(dba)3 (4.0 mg, 0.0044 mmol), xantphos (6.9 mg, 0.012 mmol) and Cs2CO3 (68 mg, 0.21 mmol). The reaction vial was sealed with an aluminum cap, and purged with N2, then dioxane (2 mL) was introduced via a syringe. The reaction mixture was then heated in a microwave oven at 150° C. for 60 minutes. The reaction mixture was cooled to room temperature, filtered, and the solvent was removed under vacuum, after which the residue was purified via chromatography on silica gel, eluting with a gradient of 0-10% methanol in dichloromethane, to give the desired product (21 mg, 40%). 1H NMR (300 MHz) δ 8.34 (d, J=2.2, 1H), 7.97 (d, J=8.9, 1H), 7.61 (dd, J=2.2, 8.9, 1H), 4.51 (dd, J=8.2, 9.7, 1H), 3.86 (m, 3H), 3.13 (m, 1H), 2.66 (m, 1H), 2.58 (m, 4H), 2.32 (m, 3H), 2.15 (ddd, J=9.5, 12.6, 19.1, 1H), 1.61 (m, 6H), 1.48 (m, 2H). MS (ESI) m/z=372.0 (M+H)+

Workup

  1. customTo a microwave vial equipped with magnetic stir bar
  2. customThe reaction
  3. customcap
  4. custompurged with N2
  5. additiondioxane (2 mL) was introduced via a syringe
  6. temperatureThe reaction mixture was cooled to room temperature
  7. filtrationfiltered
  8. customthe solvent was removed under vacuum
  9. customafter which the residue was purified via chromatography on silica gel
  10. washeluting with a gradient of 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-f51d51fad564484bbfe0b583e9c6ec4f
Source dataset
uspto-grants-2015_11
Patent number
US09186353B2

Reaction notes

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