Trifluoroacetic acid → HCID 117843078, compound

HRID 2209185Notes

Reaction equation

HRID 2209185 reaction equation
C(O)(C(F)(F)F)=O.[N:8]1([C:14]2[CH:15]=[CH:16][C:17]([C:20]3[CH:21]=[C:22]([O:29][C@@H:30]([C@H:32]4[CH2:36][NH:35][C:34](=[O:37])[CH2:33]4)[CH3:31])[C:23]4[S:27][CH:26]=[N:25][C:24]=4[CH:28]=3)=[N:18][CH:19]=2)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.CCN(C(C)C)C(C)C.[O:47]1[CH2:50][C:49](=O)[CH2:48]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.O.C([O-])(O)=O.[Na+].CCOC(C)=O>[O:47]1[CH2:50][CH:49]([N:11]2[CH2:10][CH2:9][N:8]([C:14]3[CH:15]=[CH:16][C:17]([C:20]4[CH:21]=[C:22]([O:29][C@@H:30]([C@H:32]5[CH2:36][NH:35][C:34](=[O:37])[CH2:33]5)[CH3:31])[C:23]5[S:27][CH:26]=[N:25][C:24]=5[CH:28]=4)=[N:18][CH:19]=3)[CH2:13][CH2:12]2)[CH2:48]1

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 150242543-OxetanoneHCID 117843721HCID 117843721, compound

Product 1

HCID 117843078HCID 117843078, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
40 °C

Procedure

The crude TFA salt of (R)-4-((R)-1-(5-(5-(piperazin-1-yl)pyridin-2-yl)benzo[d]thiazol-7-yloxy)ethyl)pyrrolidin-2-one (4.23) described above (0.06 mmol) was dissolved in THF (1 mL) and iPr2NEt (21 μL, 0.12 mmol) was added followed by oxetan-3-one (12 μL, 0.21 mmol) and sodium triacetoxyborohydride (55 mg, 0.26 mmol). The reaction mixture was stirred at 40° C. for 1.5 h and was diluted with water (1 mL), saturated aqueous NaHCO3 (1 mL), and EtOAc (2 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (3×1.5 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated to afford a crude residue that was purified by silica gel chromatography (0-25% MeOH in DCM) to yield (R)-4-((R)-1-(5-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)benzo[d]thiazol-7-yloxy)ethyl)pyrrolidin-2-one (4.25). LCMS-ESI+ (m/z): [M+H]+ calcd for C25H30N5O3S: 480.2; found: 479.8. 1H NMR (400 MHz, Chloroform-d) δ 9.00-8.95 (m, 1H), 8.43-8.37 (m, 1H), 8.21-8.15 (m, 1H), 7.79-7.69 (m, 2H), 7.31 (dd, J=8.4, 3.8 Hz, 1H), 5.81 (s, 1H), 4.89-4.75 (m, 1H), 4.75-4.63 (m, 4H), 3.65-3.43 (m, 2H), 3.41-3.30 (m, 5H), 3.01-2.81 (m, 1H), 2.62-2.41 (m, 6H), 1.48-1.38 (m, 3H).

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with EtOAc (3×1.5 mL)
  3. dry with materialThe combined organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford a crude residue that
  7. customwas purified by silica gel chromatography (0-25% MeOH in DCM)

Sources & evidence

ORD record
ord-5913d9de68ca451aa8d3bf66b54826d0
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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