N,N-Dimethylglycine → (S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(2-(dimethylamino)acetamido)thiazole-4-carboxamide

HRID 872578ノート

反応式

HRID 872578 の反応式
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C@@H:10]([CH3:26])[CH2:11][N:12]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[C:19]([Cl:25])[CH:18]=3)=[N:13]2)=[O:8])[N:6]=1.[CH3:27][N:28]([CH3:33])[CH2:29][C:30](O)=[O:31].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl>[Cl:25][C:19]1[CH:18]=[C:17]([C:14]2[CH:15]=[CH:16][N:12]([CH2:11][C@@H:10]([NH:9][C:7]([C:5]3[N:6]=[C:2]([NH:1][C:30](=[O:31])[CH2:29][N:28]([CH3:33])[CH3:27])[S:3][CH:4]=3)=[O:8])[CH3:26])[N:13]=2)[CH:22]=[CH:21][C:20]=1[C:23]#[N:24]

参加物

7

反応物 5

HCID 673N,N-Dimethylglycine3 回HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide3 回HCID 757711-Hydroxybenzotriazole2 回HCID 81531Diisopropylethylamine3 回HCID 86670238(S)-2-amino-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)thiazole-4-carboxamide

生成物 1

HCID 86670243(S)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-2-(2-(dimethylamino)acetamido)thiazole-4-carboxamide収率 6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A solution of (S)-2-amino-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)thiazole-4-carboxamide of Example 57 (46 mg, 0.12 mmol) in 1 ml of DCM was added to a suspension of N,N-dimethylglycine (25 mg, 0.24 mmol), DIPEA (0.041 ml; 0.24 mmol), anhydrous HOBt (32 mg, 0.24 mmol) and EDCI (46 mg, 0.24 mmol) in 1 ml of DCM. The reaction mixture was stirred at RT over three nights. N,N-dimethylglycine (25 mg), DIPEA (0.021 ml), anhydrous HOBt (16 mg) and EDCI (23 mg) were added to the reaction mixture, and stirring was continued overnight. N,N-dimethylglycine (25 mg), DIPEA (0.082 ml) and EDCI (46 mg) were added twice the following two days. Three days after last addition of reagents the reaction was quenched by adding DCM and washing 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: silica, eluent: 20-100% EtOAc in heptane) to obtain 3.2 mg (6%) of the title compound. 1H-NMR (400 MHz; CDCl3): δ 1.26 (d, 3H), 2.42 (s, 6H), 3.25 (s, 2H), 4.32 (dd, 1H), 4.42 (dd, 1H), 4.53-4.63 (m, 1H), 6.62 (d, 1H), 7.49 (d, 1H), 7.62 (d, 1H), 7.68 (d, 1H), 7.78 (s, 1H), 7.82 (dd, 1H), 7.96 (d, 1H).

後処理

  1. stirringstirring
  2. additionThree days after last addition of reagents the reaction
  3. customwas quenched
  4. additionby adding DCM
  5. washwashing with water
  6. dry with materialOrganic phase was dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customCrude product was purified twice by CombiFlash (1st column: silica, eluent: 0-10% MeOH in DCM; 2nd column: silica, eluent: 20-100% EtOAc in heptane)

出典と根拠

ORDレコード
ord-f82cd3eb676440a4bb596862a4bc8e18
出典データセット
uspto-grants-2015_03
特許番号
US08975254B2

反応ノート

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