Dimethylformamide → (S)-5-(((4-(Trifluoromethyl)phenyl)(3-(trifluoromethyl)-pyridin-2-yl)methyl)carbamoyl)picolinic Acid 2,2,2-trifluoroacetate

HRID 509370

反応式

HRID 509370 の反応式
C[O:2][C:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][N:6]=1)=[O:4].CCN(C(C)C)C(C)C.CN(C([O:30]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[F:48][C:49]([F:69])([F:68])[C:50]1[CH:55]=[CH:54][C:53]([C@@H:56]([C:58]2[C:63]([C:64]([F:67])([F:66])[F:65])=[CH:62][CH:61]=[CH:60][N:59]=2)[NH2:57])=[CH:52][CH:51]=1.CN([CH:73]=[O:74])C>C1COCC1.CO.[Li+].[OH-]>[F:48][C:49]([F:69])([F:68])[C:73]([OH:74])=[O:30].[F:68][C:49]([F:48])([F:69])[C:50]1[CH:51]=[CH:52][C:53]([C@H:56]([NH:57][C:9]([C:8]2[CH:12]=[CH:13][C:5]([C:3]([OH:2])=[O:4])=[N:6][CH:7]=2)=[O:11])[C:58]2[C:63]([C:64]([F:65])([F:66])[F:67])=[CH:62][CH:61]=[CH:60][N:59]=2)=[CH:54][CH:55]=1

参加物

9

反応物 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 5796316-(Methoxycarbonyl)pyridine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86687962(S)-(4-(Trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)methanamine Hydrochloride2 回

生成物 1

HCID 86687979(S)-5-(((4-(Trifluoromethyl)phenyl)(3-(trifluoromethyl)-pyridin-2-yl)methyl)carbamoyl)picolinic Acid 2,2,2-trifluoroacetate

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 3939Lithium Hydroxide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 6-(methoxycarbonyl)nicotinic acid (58.4 mg, 0.322 mmol) and DIPEA (0.20 mL, 1.148 mmol) in DMF (2 mL) were added HATU (178 mg, 0.468 mmol) and (S)-(4-(trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)-methanamine hydrochloride (Intermediate 1) (100 mg, 0.312 mmol). The solution was stirred at rt for 2 h. The solution was then diluted with THF (10 mL), MeOH (3 mL), and 1M LiOH (2 mL). After a further 16 h, the reaction was concentrated in vacuo, taken up in a minimum of DMF and purified by reverse-phase preparative HPLC (Shimadzu) on a Phenomenex Gemini™ column (5 micron, C18, 110 Å, Axia, 100×30 mm) eluting at 45 mL/min with a linear gradient of 20% to 90% MeCN (0.1% TFA) in H2O (0.1% TFA) over 10 minutes to the title compound as a yellow solid. 1H NMR (CDCl3, 300 MHz) δ ppm 9.14 (s, 1H), 8.94 (d, J=4.4 Hz, 1H), 8.64 (d, J=7.2 Hz, 1H), 8.41 (d, J=8.0 Hz, 1H), 8.25 (d, J=7.9 Hz, 1H), 8.13 (d, J=7.9 Hz, 1H), 7.46-7.63 (m, 5H), 6.88 (d, J=7.0 Hz, 1H). MS (ESI pos. ion) m/z: 469.9 (M+H).

後処理

  1. waitAfter a further 16 h
  2. concentrationthe reaction was concentrated in vacuo
  3. custompurified by reverse-phase preparative HPLC (Shimadzu) on a Phenomenex Gemini™ column (5 micron, C18, 110 Å, Axia, 100×30 mm)
  4. washeluting at 45 mL/min with a linear gradient of 20% to 90% MeCN (0.1% TFA) in H2O (0.1% TFA) over 10 minutes to the title compound as a yellow solid

出典と根拠

ORDレコード
ord-9b7c888ede954fdeb52a534fb085c6b5
出典データセット
uspto-grants-2015_08
特許番号
US09096527B2

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