Cesium carbonate → HCID 42629727, compound

HRID 1880615Notes

Reaction equation

HRID 1880615 reaction equation
[N:1]1([C:7]2[C:12](/[CH:13]=[CH:14]/[C:15](O)=[O:16])=[CH:11][CH:10]=[C:9]([C:18]([F:21])([F:20])[F:19])[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br.[Cl:29][C:30]1[C:39]([OH:40])=[C:38]([OH:41])[C:37]([Cl:42])=[C:36]2[C:31]=1[CH2:32][CH2:33][NH:34][CH2:35]2.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>C1COCC1.CN(C1C=CN=CC=1)C.O>[Cl:29][C:30]1[C:39]([OH:40])=[C:38]([OH:41])[C:37]([Cl:42])=[C:36]2[C:31]=1[CH2:32][CH2:33][N:34]([C:15](=[O:16])/[CH:14]=[CH:13]/[C:12]1[C:7]([N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[N:8][C:9]([C:18]([F:21])([F:20])[F:19])=[CH:10][CH:11]=1)[CH2:35]2

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59830359HCID 59830359, compoundHCID 685081725,8-Dichloro-1,2,3,4-tetrahydroisoquinoline-6,7-diol--hydrogen bromide (1/1)

Product 1

HCID 42629727HCID 42629727, compoundYield 24%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

(E)-3-(2-(piperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)acrylic acid (150.0 mg, 0.50 mmol) was suspended in dry THF (7.0 mL). DMAP (111.4 mg, 0.91 mmol) and caesium carbonate (296.0 mg, 0.91 mmol) were added and the mixture was stirred at rt for 15 minutes. 5,8-Dichloro-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrobromide (143.0 mg, 0.45 mmol), EDC.HCl (130.6 mg, 0.68 mmol), HOBt (69.8 mg, 0.45 mmol) were then added. The mixture was stirred at rt overnight. Water (100 mL) was added and the product extracted with EtOAc. Combined organic extracts were dried (MgSO4), filtered and concentrated. Purification was done first using flash column chromatography (CH2Cl2/MeOH 98/2→95/5) and then by size exclusion (Sephadex LH20; CHCl3/MeOH 1/1) to yield 55.0 mg (24%) of the title product.

Workup

  1. stirringThe mixture was stirred at rt overnight
  2. extractionthe product extracted with EtOAc
  3. dry with materialCombined organic extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification

Sources & evidence

ORD record
ord-a3d0ff963d8c42e6b5cedb6d58ebf1af
Source dataset
uspto-grants-2012_11
Patent number
US08318768B2

Reaction notes

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