Diisopropylethylamine → HCID 86687975, compound

HRID 509366Notes

Reaction equation

HRID 509366 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([C:11]([OH:13])=O)=[N:9][CH:10]=1)=[O:4].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.[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(C=O)C.C1COCC1.CO.[Li+].[OH-]>[F:68][C:49]([F:48])([F:69])[C:50]1[CH:51]=[CH:52][C:53]([C@H:56]([NH:57][C:11]([C:8]2[CH:7]=[CH:6][C:5]([C:3]([OH:2])=[O:4])=[CH:10][N:9]=2)=[O:13])[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

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 3149925-(Methoxycarbonyl)pyridine-2-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×

Product 1

HCID 86687975HCID 86687975, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3939Lithium HydroxideSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(methoxycarbonyl)picolinic acid (70.7 mg, 0.390 mmol) and DIPEA (0.20 mL, 1.148 mmol) in DMF (2 mL) were added HATU (223 mg, 0.586 mmol) and (S)-(4-(trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)-methanamine hydrochloride (Intermediate 1) (125 mg, 0.390 mmol). The resulting mixture was stirred at rt 16 h. The mixture 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 give the title compound as a white solid after lyopholization. 1H NMR (CDCl3, 300 MHz) δ ppm 9.74 (d, J=8.2 Hz, 1H), 9.25 (s, 1H), 8.97 (d, J=4.0 Hz, 1H), 8.47 (dd, J=8.0, 2.1 Hz, 1H), 8.26 (d, J=8.8 Hz, 1H), 8.04 (d, J=8.0 Hz, 1H), 7.61 (d, J=8.5 Hz, 2H), 7.55 (d, J=8.5 Hz, 2H), 7.46 (dd, J=7.5, 5.0 Hz, 1H), 6.88 (d, J=8.2 Hz, 1H). MS (ESI pos. ion) m/z: 469.9 (M+H).

Workup

  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

Sources & evidence

ORD record
ord-6c33eee3b72d4859af71a8011fbf00f3
Source dataset
uspto-grants-2015_08
Patent number
US09096527B2

Reaction notes

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