3-Hydroxy-2,2-dimethylpropionic acid → HCID 68688264, compound

HRID 1992159Notes

Reaction equation

HRID 1992159 reaction equation
[CH:1]([C:4]1[CH:5]=[C:6]([Mg]Br)[CH:7]=[CH:8][CH:9]=1)([CH3:3])[CH3:2].C(C(=C1CCN(C(OC(C)(C)C)=O)CC1)C(OCC)=O)#N.[OH:33][CH2:34][C:35]([CH3:40])([CH3:39])[C:36](O)=[O:37].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.C(C1C=C([C:84]2([CH2:90][CH2:91][N:92]3[CH:97]4[CH2:98][CH2:99][CH:93]3[CH2:94][CH:95]([N:100]3[C:104]5[CH:105]=[CH:106][CH:107]=[CH:108][C:103]=5[N:102]=[C:101]3[CH3:109])[CH2:96]4)[CH2:89][CH2:88][NH:87][CH2:86][CH2:85]2)C=CC=1)(C)C>CN(C=O)C.CCOC(C)=O>[CH:1]([C:4]1[CH:5]=[C:6]([C:84]2([CH2:90][CH2:91][N:92]3[CH:97]4[CH2:98][CH2:99][CH:93]3[CH2:94][CH:95]([N:100]3[C:104]5[CH:105]=[CH:106][CH:107]=[CH:108][C:103]=5[N:102]=[C:101]3[CH3:109])[CH2:96]4)[CH2:89][CH2:88][N:87]([C:36](=[O:37])[C:35]([CH3:40])([CH3:39])[CH2:34][OH:33])[CH2:86][CH2:85]2)[CH:7]=[CH:8][CH:9]=1)([CH3:3])[CH3:2]

Participants

9

Reactant 6

HCID 785483-Hydroxy-2,2-dimethylpropionic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11551073TERT-BUTYL 4-(1-CYANO-2-ETHOXY-2-OXOETHYLIDENE)PIPERIDINE-1-CARBOXYLATEHCID 68716332HCID 68716332, compoundHCID 178439132HCID 178439132, compound

Product 1

HCID 68688264HCID 68688264, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

This compound was prepared from 3-isopropyl phenylmagnesium bromide and 16a according to the procedure described in example 16. To a solution of 3-hydroxy-2,2-dimethylpropanoic acid (0.14 mmol), DIEA (1.7 mmol) and HATU (0.14 mmol) in DMF was added 1-(8-{2-[4(-3-isopropylphenyl)piperdin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole hydrochloride (0.13 mmol) in the same solvent and stirring was continued overnight. The reaction mixture was diluted with EtOAc, and washed with NaHCO3, water, and satd. brine and dried (Na2SO4). The solvent was removed in-vacuo and the crude material was purified by HPLC to 1 as a clear film. H NMR (400 MHz, CDCl3) 9.72 (s, 2H), 8.48 (s, 1H), 7.64 (d, 1H), 7.04-7.36 (m, 8H), 4.74 (t, 1H), 3.19-3.32 (m, 4H), 2.88-2.97 (m, 3H), 2.60 (s, 3H), 2.43-2.47 (d, 4H), 2.37 (s, 2H), 1.86-2.33 (m, 10H), 1.77 (d, 2H), 1.26-1.28 (d, 6H). LCMS m/z (M+H) calc: 556.79, obsd: 557.79.

Workup

  1. washwashed with NaHCO3, water
  2. dry with materialbrine and dried (Na2SO4)
  3. customThe solvent was removed in-vacuo
  4. customthe crude material was purified by HPLC to 1 as a clear film

Sources & evidence

ORD record
ord-3dbf96bd56f64344862c437de88aaf08
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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