Dimethylformamide → HCID 68183093, compound

HRID 1615574Notes

Reaction equation

HRID 1615574 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@H:13]([C:14]([OH:16])=O)[NH:12][C:11](=[O:17])[C:10]3[S:18][C:19]([C:21]4[CH:26]=[CH:25][N:24]=[C:23]([CH3:27])[CH:22]=4)=[CH:20][C:9]2=3)=[CH:4][CH:3]=1.[CH3:28][N:29](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C)C=O.CN.O1CCCC1.C(N(CC)C(C)C)(C)C>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]2[C@H:13]([C:14]([NH:29][CH3:28])=[O:16])[NH:12][C:11](=[O:17])[C:10]3[S:18][C:19]([C:21]4[CH:26]=[CH:25][N:24]=[C:23]([CH3:27])[CH:22]=4)=[CH:20][C:9]2=3)=[CH:6][CH:7]=1

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 6329MethylamineHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68182964HCID 68182964, compound

Product 1

HCID 68183093HCID 68183093, compoundYield 41.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of rel-(4R,5R)-4-(4-chlorophenyl)-2-(2-methylpyridin-4-yl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylic acid (326.0 mg, 0.817 mmol) and HATU (435.1 mg, 1.144 mmol) in N,N-dimethylformamide (4.28 mL, 55.3 mmol) were added methylamine as a 2M solution in tetrahydrofuran (1.64 mL, 3.27 mmol) followed by N,N-diisopropylethylamine (0.427 mL, 2.45 mmol). The mixture was stirred at rt for 16 hr. The mixture was diluted with water (4 mL) and the precipitate was filtered. The aqueous solution was extracted with DCM (3×6 mL). The solid cake and DCM layers were combined and washed with water (3 mL) and brine (3 mL), dried over sodium sulfate, and evaporated. The obtained residue purified by preparative HPLC to give the title compound as a white solid (140 mg) then the racemic mixture was separated by chiral preparative HPLC to give 30.6 mg (9.0% yield) as a white solid for peak 1. LCMS: (FA) ES+ , 412/414. 1H NMR (400 MHz, DMSO) δ 8.46 (d, J=5.3 Hz, 1H), 8.16 (d, J=4.4 Hz, 1H), 7.94 (d, J=4.2 Hz, 1H), 7.62 (s, 1H), 7.55 (s, 1H), 7.49-7.37 (m, 3H), 7.25 (d, J=8.5 Hz, 2H), 4.66 (d, J=1.6 Hz, 1H), 4.14 (dd, J=4.2, 2.3 Hz, 1H), 2.59 (d, J=4.5 Hz, 3H). 37.0 mg (11% yield) as a white solid for peak 2. LCMS: (FA) ES+ , 412. 1H NMR (400 MHz, DMSO) δ 8.46 (d, J=5.2 Hz, 1H), 8.16 (d, J=4.4 Hz, 1H), 7.95 (d, J=4.3 Hz, 1H), 7.62 (s, 1H), 7.55 (s, 1H), 7.50-7.35 (m, 3H), 7.25 (d, J=8.5 Hz, 2H), 4.66 (d, J=1.8 Hz, 1H), 4.14 (dd, J=4.3, 2.3 Hz, 1H), 2.59 (d, J=4.5 Hz, 3H).

Workup

  1. filtrationthe precipitate was filtered
  2. extractionThe aqueous solution was extracted with DCM (3×6 mL)
  3. washwashed with water (3 mL) and brine (3 mL)
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customThe obtained residue purified by preparative HPLC

Sources & evidence

ORD record
ord-6672b031eacd4e479f9ddd083aae27e0
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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