Dichloromethane → HCID 178464737, compound

HRID 2059839Notes

Reaction equation

HRID 2059839 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:32][CH2:31][CH2:30][C@@:10]3([C:14](=[O:15])[N:13]([C@H:16]4[CH2:21][CH2:20][C@@H:19]([O:22][Si](C(C)(C)C)(C)C)[CH2:18][CH2:17]4)[CH2:12][CH2:11]3)[CH2:9]2)=[C:4]([Cl:33])[CH:3]=1.ClCCl.C(=O)([O-])[O-].[K+].[K+].[CH2:43]([NH:45][C:46]([C:48]1[CH:53]=[CH:52][C:51](B2OC(C)(C)C(C)(C)O2)=[CH:50][N:49]=1)=[O:47])[CH3:44]>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:33][C:4]1[CH:3]=[C:2]([C:51]2[CH:52]=[CH:53][C:48]([C:46]([NH:45][CH2:43][CH3:44])=[O:47])=[N:49][CH:50]=2)[CH:7]=[CH:6][C:5]=1[N:8]1[CH2:32][CH2:31][CH2:30][C@@:10]2([C:14](=[O:15])[N:13]([C@H:16]3[CH2:21][CH2:20][C@@H:19]([OH:22])[CH2:18][CH2:17]3)[CH2:12][CH2:11]2)[CH2:9]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 59868917N-ethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamideHCID 178455329HCID 178455329, compound

Product 1

HCID 178464737HCID 178464737, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a stirred mixture of (5S)-7-(4-bromo-2-chlorophenyl)-2-(cis-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-2,7-diazaspiro[4.5]decan-1-one (20 mg, 0.00004 mol), [1,1 ′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (2.0 mg), tetrakis(triphenylphosphine)palladium (1.0 mg) and potassium carbonate (14.9 mg, 0.000108 mol) in anhydrous N,N-dimethylformamide (1 mL) was added N-ethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxamide (14.5 mg, 0.054 mmol). The resulting reaction mixture was heated at 150° C. and stirred overnight, followed by the removal of TBS protecting group by the addition of 1.7 M of fluorosilicic acid in water (0.10 mL) and the mixture was stirred at r.t. overnight. The reaction mixture was then directly purified by RP-HPLC to afford the desired product. LC/MS m/e 511.2 (M+H)+. 1H-NMR (400 MHz, DMSO-d6): 8.92 (1H, d, J=2.3 Hz), 8.84 (1H, t, J=5.9 Hz), 8.26 (1H, dd, J=8.2, 2.3 Hz), 8.06 (1H, d, J=8.2 Hz), 7.89 (1H, d, J=2.2 Hz), 7.74 (1H, dd, J=8.5, 2.2 Hz), 7.30 (1H, t, J=8.5 Hz), 4.39 (1 H, d, J=3.1 Hz), 3.80 (1H, m), 3.72 (1H, m), 3.24-3.44 (5H, m), 3.01 (1H, d, J=11.4 Hz), 2.63-2.74 (2H, m), 2.40-2.53 (1H, m), 1.64-1.91 (8H, m), 1.41-1.53 (3H, m), 1.20-1.32 (2H, m), 1.13 (3H, t, J=7.2 Hz).

Workup

  1. customThe resulting reaction mixture
  2. customfollowed by the removal of TBS protecting group by the addition of 1.7 M of fluorosilicic acid in water (0.10 mL)
  3. stirringthe mixture was stirred at r.t. overnight
  4. customThe reaction mixture was then directly purified by RP-HPLC

Sources & evidence

ORD record
ord-96e8eff07a474cd2af4c873967c964b6
Source dataset
uspto-grants-2012_10
Patent number
US08278318B2

Reaction notes

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