N,N-Dimethylglycine → HCID 11684354, compound

HRID 646908Notes

Reaction equation

HRID 646908 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[C:12]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[CH:11]=[CH:10][C:9]=2[NH:20][C:21]([C:23]2[NH:24][CH:25]=[C:26]([C:28]#[N:29])[CH:27]=2)=[O:22])[CH2:4][CH2:3]1.FC(F)(F)C(O)=O.[OH-].[Na+].CO.[CH3:41][N:42]([CH3:47])[CH2:43][C:44](O)=[O:45].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O>[CH3:41][N:42]([CH3:47])[CH2:43][C:44]([N:17]1[CH2:18][CH2:19][CH:14]([C:12]2[CH:11]=[CH:10][C:9]([NH:20][C:21]([C:23]3[NH:24][CH:25]=[C:26]([C:28]#[N:29])[CH:27]=3)=[O:22])=[C:8]([N:5]3[CH2:6][CH2:7][CH:2]([CH3:1])[CH2:3][CH2:4]3)[CH:13]=2)[CH2:15][CH2:16]1)=[O:45]

Participants

10

Reactant 7

HCID 673N,N-DimethylglycineHCID 6422Trifluoroacetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11671730HCID 11671730, compoundHCID 23721981Sodium hydroxide methanol

Product 1

HCID 11684354HCID 11684354, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of 4-cyano-1H-pyrrole-2-carboxylic acid [2-(4-methyl-piperidin-1-yl)-4-piperidin-4-yl-phenyl]-amide bis(trifluoroacetic acid salt) (as prepared in Example 35, 20.0 mg, 0.0320 mmol) in 2 mL of 1:1 1N NaOH/MeOH solution was stirred at RT for 1 h. Treated with 20 mL of EtOAc, the mixture was washed with H2O (3×5 mL). The aqueous layers were extracted with EtOAc (2×5 mL). The combined organic layers were washed with brine (10 mL), dried (Na2SO4) and concentrated in vacuo to give a white solid. The solid was added to a mixture of N,N-dimethylglycine (5.0 mg, 0.048 mmol), EDCI (9.2 mg, 0.048 mmol), HOBt (6.5 mg, 0.048 mmol) and DIEA (16.7 μL, 0.096 mmol) in 0.80 mL of DCM. The resulting mixture was stirred at RT for 4 h. Treated with 30 mL of EtOAc, the mixture was washed with H2O (3×5 mL), brine (5 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (1-5% MeOH/DCM) gave 12 mg (78%) of the title compound as a white solid: 1H-NMR (CDCl3; 400 MHz): δ 11.0 (s, 1H), 9.17 (s, 1H), 8.31 (d, 1H, J=8.4 Hz), 7.48 (d, 1H, J=1.3 Hz), 7.05 (d, 1H, J=1.8 Hz), 7.01 (dd, 1H, J=8.4, 1.8 Hz), 6.87 (d, 1H, J=1.3 Hz), 4.77 (d, 1H, J=13.3 Hz), 4.24 (d, 1H, J=13.3 Hz), 3.07-3.25 (m, 3H), 2.96 (d, 2H, J=11.8 Hz), 2.61-2.77 (m, 4H), 2.33 (s, 6H), 1.82-1.94 (m, 4H), 1.53-1.70 (m, 3H), 1.32-1.47 (m, 2H), 1.09 (d, 3H, J=6.5 Hz). Mass spectrum (ESI, m/z): Calcd. for C27H36N6O2, 477.3 (M+H), found 477.2.

Workup

  1. washthe mixture was washed with H2O (3×5 mL)
  2. extractionThe aqueous layers were extracted with EtOAc (2×5 mL)
  3. washThe combined organic layers were washed with brine (10 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customto give a white solid
  7. stirringThe resulting mixture was stirred at RT for 4 h
  8. washthe mixture was washed with H2O (3×5 mL), brine (5 mL)
  9. dry with materialdried (Na2SO4)
  10. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-68f6b9ab676c499caf74690d863ad99f
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Reaction notes

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