N,N-Dimethylglycine → 4-Cyano-1h-pyrrole-2-carboxylic acid (2-cyclohex-1-enyl-4-[1-(2-dimethylamino-acetyl)-piperidin-4-yl]-phenyl)-amide trifluoroacetic acid salt

HRID 1992041Notes

Reaction equation

HRID 1992041 reaction equation
[CH3:1][N:2]([CH2:4][C:5]([OH:7])=O)[CH3:3].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.C(N(CC)CC)C.[F:30][C:31]([F:36])([F:35])[C:32]([OH:34])=[O:33].[C:37]1([C:43]2[CH:48]=[C:47]([CH:49]3[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]3)[CH:46]=[CH:45][C:44]=2[NH:55][C:56]([C:58]2[NH:59][CH:60]=[C:61]([C:63]#[N:64])[CH:62]=2)=[O:57])[CH2:42][CH2:41][CH2:40][CH2:39][CH:38]=1>C(Cl)Cl>[F:30][C:31]([F:36])([F:35])[C:32]([OH:34])=[O:33].[C:37]1([C:43]2[CH:48]=[C:47]([CH:49]3[CH2:50][CH2:51][N:52]([C:5](=[O:7])[CH2:4][N:2]([CH3:3])[CH3:1])[CH2:53][CH2:54]3)[CH:46]=[CH:45][C:44]=2[NH:55][C:56]([C:58]2[NH:59][CH:60]=[C:61]([C:63]#[N:64])[CH:62]=2)=[O:57])[CH2:42][CH2:41][CH2:40][CH2:39][CH:38]=1

Participants

6

Reactant 4

HCID 673N,N-DimethylglycineHCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 116055404-Cyano-1h-pyrrole-2-carboxylic acid (2-cyclohex-1-enyl-4-piperidin-4-yl-phenyl)-amide trifluoroacetic acid salt

Product 1

HCID 866073614-Cyano-1h-pyrrole-2-carboxylic acid (2-cyclohex-1-enyl-4-[1-(2-dimethylamino-acetyl)-piperidin-4-yl]-phenyl)-amide trifluoroacetic acid saltYield 99.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A suspension of 9.10 mg (0.0881 mmol) dimethylamino-acetic acid in 5 mL CH2Cl2 was treated with 21.7 mg (0.0852 mmol) BOP—Cl and 32.8 μL (0.235 mmol) triethylamine at RT for 50 min. This mixture was added to a suspension of 22.0 mg (0.0588 mmol) 4-cyano-1H-pyrrole-2-carboxylic acid (2-cyclohex-1-enyl-4-piperidin-4-yl-phenyl)-amide trifluoroacetic acid salt (as prepared in the previous step) in 5 mL CH2Cl2. The mixture stirred at RT for 23 h, was diluted with CH2Cl2 (15 mL), and washed with saturated aqueous NaHCO3 (1×10 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. Purification of the residue by RP-HPLC (C18) with 20-80% CH3CN in 0.1% TFA/H2O over 30 min to afford 33.6 mg (83%) of the title compound as a white solid: 1H-NMR (CD3OD; 400 MHz): δ 7.54 (d, 1H, J=1.6 Hz), 7.41 (d, 1H, J=8.0 Hz), 7.14 (dd, 1H, J=8.4 Hz, J=2.0 Hz), 7.12-7.08 (m, 1H), 7.07 (d, 1H, J=2.0 Hz), 5.70-5.65 (m, 1H), 4.67-4.59 (m, 1H), 4.26 (q, 2H, J=16.4 Hz), 3.78-3.70 (m, 1H), 3.26-3.17 (m, 1H), 2.97-2.89 (m, 6H), 2.88-2.75 (m, 2H), 2.25-2.18 (m, 2H), 2.15-2.07 (m, 2H), 1.94-1.85 (m, 2H), 1.76-1.54 (m, 6H). Mass spectrum (ESI, m/z): Calcd. for C27H33N5O2, 460.3 (M+H), found 460.3.

Workup

  1. washwashed with saturated aqueous NaHCO3 (1×10 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customPurification of the residue by RP-HPLC (C18) with 20-80% CH3CN in 0.1% TFA/H2O over 30 min

Sources & evidence

ORD record
ord-11e61de18533435b95410d333806467b
Source dataset
uspto-grants-2010_01
Patent number
US07645755B2

Reaction notes

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