N,N-Dimethylglycine → HCID 178472708, compound

HRID 872576Notes

Reaction equation

HRID 872576 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[NH:25][N:24]=[C:23]([CH:26]([OH:28])[CH3:27])[CH:22]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[CH3:29][N:30]([CH3:35])[CH2:31][C:32](O)=[O:33].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl>[CH3:29][N:30]([CH3:35])[CH2:31][C:32]([O:28][CH:26]([C:23]1[CH:22]=[C:21]([C:19](=[O:20])[NH:18][C@@H:16]([CH3:17])[CH2:15][N:12]2[CH:13]=[CH:14][C:10]([C:4]3[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[CH:3]=3)=[N:11]2)[NH:25][N:24]=1)[CH3:27])=[O:33]

Participants

7

Reactant 5

HCID 673N,N-DimethylglycineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 178466823HCID 178466823, compound

Product 1

HCID 178472708HCID 178472708, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of N—((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-3-(1-hydroxyethyl)-1H-pyrazole-5-carboxamide of Example 56 (90 mg, 0.225 mmol) in 2 ml of DCM was added to a suspension of N,N-dimethylglycine (47 mg, 0.45 mmol), DIPEA (0.13 ml; 0.75 mmol), anhydrous HOBt (61 mg, 0.45 mmol) and EDCI (87 mg, 0.45 mmol) in 2 ml of DCM. The reaction mixture was stirred at RT over three nights. The mixture was diluted with DCM and washed with water. Organic phase was dried over Na2SO4, filtered and evaporated. Crude product was purified twice by CombiFlash (1st column: silica, eluent: 0-10% MeOH in DCM; 2nd column: alumina, eluent: 0-10% MeOH in DCM) to obtain 26 mg (36%) of the title compound. 1H-NMR (400 MHz; CDCl3): δ 1.22 (d, 3H), 1.66 (d, 3H), 2.35 (d, 6H), 3.20 (d, 2H), 4.25-4.33 (m, 1H), 4.37-4.45 (m, 1H), 4.52-4.64 (m, 1H), 6.00 (q, 1H), 6.60 (m, 1H), 6.80 (s, 1H), 7.50 (dd, 1H), 7.67 (m, 1H), 7.74-7.87 (m, 2H), 8.09 (d, 1H), 11.6 (bs, 1H).

Workup

  1. washwashed with water
  2. dry with materialOrganic phase was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customCrude product was purified twice by CombiFlash (1st column: silica, eluent: 0-10% MeOH in DCM; 2nd column: alumina, eluent: 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-daa083fbb28a469cb9ea30e6e138d5a9
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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