Trifluoroacetic acid → N-[(1R,6R)-6-Amino-2,2-difluorocyclohexyl]-4-(imidazo[1,2-b]pyridazin-3-yl)-5-methylthiophene-2-carboxamide

HRID 2046404ノート

反応式

HRID 2046404 の反応式
[N:1]1[CH:2]=[C:3]([C:10]2[CH:11]=[C:12]([C:16]([OH:18])=O)[S:13][C:14]=2[CH3:15])[N:4]2[C:9]=1[CH:8]=[CH:7][CH:6]=[N:5]2.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(OC(=O)[NH:52][C@@H:53]1[CH2:58][CH2:57][CH2:56][C:55]([F:60])([F:59])[C@@H:54]1[NH2:61])(C)(C)C.C(N(C(C)C)CC)(C)C.FC(F)(F)C(O)=O>O.ClCCl>[NH2:52][C@H:53]1[C@@H:54]([NH:61][C:16]([C:12]2[S:13][C:14]([CH3:15])=[C:10]([C:3]3[N:4]4[N:5]=[CH:6][CH:7]=[CH:8][C:9]4=[N:1][CH:2]=3)[CH:11]=2)=[O:18])[C:55]([F:60])([F:59])[CH2:56][CH2:57][CH2:58]1

参加物

8

反応物 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 580464044-(Imidazo[1,2-b]pyridazin-3-yl)-5-methylthiophene-2-carboxylic acidHCID 59603811tert-Butyl ((1R,2R)-2-amino-3,3-difluorocyclohexyl)carbamate

生成物 1

HCID 67123022N-[(1R,6R)-6-Amino-2,2-difluorocyclohexyl]-4-(imidazo[1,2-b]pyridazin-3-yl)-5-methylthiophene-2-carboxamide

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

To a mixture of 4-(imidazo[1,2-b]pyridazin-3-yl)-5-methylthiophene-2-carboxylic acid (0.06 g, 0.24 mmol) and BOP (0.16 g, 0.36 mmol) was added tert-butyl[(1R,2R)-2-amino-3,3-difluorocyclohexyl]carbamate (0.06 g, 0.26 mmol) followed by diisopropylethylamine (0.09 mL, 0.49 mmol). The mixture was allowed stir at room temperature overnight. The resulting solution was diluted with water and extracted three times with dichloromethane. The combined organic layers were dried with magnesium sulfate, filtered, concentrated and to the resulting residue was added dichloromethane and trifluoroacetic acid (1 mL, 53 mmol). The compound was purified by prep HPLC. The compound was neutralized by taking the fractions and adding an aqueous saturated sodium bicarbonate solution and extracting three times with ethyl acetate. The combined organics were dried with magnesium sulfate, filtered, and concentrated to afford the title compound as a yellow solid. 1H NMR (500 MHz, CD3SOCD3) δ 8.62 (d, 1H); 8.28 (s, 1H); 8.21 (d, 1H); 7.99 (s, 1H); 7.90 (d, 1H); 7.29 (dd, 1H); 4.55 (m, 1H); 3.08 (m, 1H); 2.47 (s, 3H); 2.11 (m, 1H); 1.85 (m, 1H); 1.71 (m, TH); 1.59 (m, 2H); 1.45 (m, 1H). LRMS (APCI) calc'd for (C18H19F2N5OS) [M+H]+, 392.1. found 392.1.

後処理

  1. extractionextracted three times with dichloromethane
  2. dry with materialThe combined organic layers were dried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated and to the resulting residue
  5. customThe compound was purified by prep HPLC
  6. additionadding an aqueous saturated sodium bicarbonate solution
  7. extractionextracting three times with ethyl acetate
  8. dry with materialThe combined organics were dried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

出典と根拠

ORDレコード
ord-e79a14bb9ee04b8991c360c531b23669
出典データセット
uspto-grants-2013_11
特許番号
US08592425B2

反応ノート

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