N,N-Dimethylglycine → HCID 178483921, compound

HRID 1428071Notes

Reaction equation

HRID 1428071 reaction equation
[CH3:1][N:2]([CH3:7])[CH2:3][C:4](O)=[O:5].O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.CCN(CC)CC.[F:30][C:31]([F:36])([F:35])[C:32]([OH:34])=[O:33].[CH3:37][C:38]1([CH3:66])[CH2:43][CH2:42][C:41]([C:44]2[N:49]=[C:48]([CH:50]3[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]3)[CH:47]=[CH:46][C:45]=2[NH:56][C:57]([C:59]2[NH:60][CH:61]=[C:62]([C:64]#[N:65])[N:63]=2)=[O:58])=[CH:40][CH2:39]1>C(Cl)Cl>[F:30][C:31]([F:36])([F:35])[C:32]([OH:34])=[O:33].[CH3:1][N:2]([CH3:7])[CH2:3][C:4]([N:53]1[CH2:54][CH2:55][CH:50]([C:48]2[CH:47]=[CH:46][C:45]([NH:56][C:57]([C:59]3[NH:60][CH:61]=[C:62]([C:64]#[N:65])[N:63]=3)=[O:58])=[C:44]([C:41]3[CH2:42][CH2:43][C:38]([CH3:66])([CH3:37])[CH2:39][CH:40]=3)[N:49]=2)[CH2:51][CH2:52]1)=[O:5]

Participants

6

Reactant 4

HCID 673N,N-DimethylglycineHCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 1784246344-cyano-1H-imidazole-2-carboxylic acid[6-(4,4-dimethyl-cyclohex-1-enyl)-1',2',3',4',5',6'-hexahydro-[2,4']bipyridinyl-5-yl]-amide trifluoroacetate

Product 1

HCID 178483921HCID 178483921, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 20.9 mg (0.203 mmol) N,N-dimethylglycine in 4 mL CH2Cl2 was treated with 49.8 mg (0.197 mmol) bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl) and 75 μL (0.54 mmol) Et3N at room temperature for 1 h. The mixture was then treated with 70.0 mg (0.135 mmol) 4-cyano-1H-imidazole-2-carboxylic acid [6-(4,4-dimethyl-cyclohex-1-enyl)-1′,2′,3′,4′,5′,6′-hexahydro-[2,4′]bipyridinyl-5-yl]-amide trifluoroacetate (as prepared in Example 54, step (f)) at room temperature for 18 h. The mixture was diluted with CH2Cl2 and washed with water. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was purified by RP-HPLC (C18) with 10-80% CH3CN in 0.1% TFA/H2O over 30 min to afford 34.9 mg (53%) of the title compound as a white solid. 1H-NMR (CD3OD; 400 MHz): δ 8.38 (d, 1H, J=8.4 Hz), 8.05 (s, 1H), 7.33 (d, 1H, J=8.4 Hz), 6.05-5.98 (m, 1H), 4.68 (d, 1H, J=15.2 Hz), 3.82 (d, 1H, J=15.2 Hz), 3.16-3.05 (m, 1H), 3.01-2.94 (m, 6H), 2.52-2.40 (m, 2H), 2.39 (s, 6H), 2.17-2.10 (m, 2H), 2.09-1.87 (m, 2H), 1.67-1.59 (m, 2H), 1.12 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C27H35N7O2, 490.3 (M+H). found 490.4.

Workup

  1. washwashed with water
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by RP-HPLC (C18) with 10-80% CH3CN in 0.1% TFA/H2O over 30 min

Sources & evidence

ORD record
ord-1c2a2f6975114c52ae79e3fa75b8325e
Source dataset
uspto-grants-2015_01
Patent number
US08933091B2

Reaction notes

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