Trifluoroacetic acid → HCID 117843076, compound

HRID 2209186Notes

Reaction equation

HRID 2209186 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[CH2:52][CH2:51][C:50](=O)[CH2:49][CH2:48]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.O.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>[O:47]1[CH2:52][CH2:51][CH:50]([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)[CH2:49][CH2:48]1

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 117843721HCID 117843721, compound

Product 1

HCID 117843076HCID 117843076, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
50 °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 dihydro-2H-pyran-4(3H)-one (28 μL, 0.30 mmol) and sodium triacetoxyborohydride (57 mg, 0.27 mmol). The reaction mixture was stirred at 50° C. for 18 h and was diluted with water (1 mL), 5% aqueous Na2CO3 (2 mL), and EtOAc (2 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (4×1.5 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-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)pyridin-2-yl)benzo[d]thiazol-7-yloxy)ethyl)pyrrolidin-2-one (4.26). LCMS-ESI+ (m/z): [M+H]+ calcd for C27H34N5O3S: 508.24; found: 508.41. 1H NMR (400 MHz, Chloroform-d) δ 8.98 (s, 1H), 8.40-8.36 (m, 1H), 8.18 (d, J=1.2 Hz, 1H), 7.77-7.72 (m, 1H), 7.71 (s, 1H), 7.29 (dd, J=8.8, 3.0 Hz, 1H), 5.84 (s, 1H), 4.88-4.74 (m, 1H), 4.10-3.99 (m, 2H), 3.57-3.49 (m, 1H), 3.46-3.35 (m, 3H), 3.34-3.29 (m, 4H), 2.97-2.85 (m, 1H), 2.80-2.74 (m, 4H), 2.62-2.43 (m, 3H), 1.86-1.78 (m, 2H), 1.69-1.56 (m, 2H), 1.44 (d, J=6.1 Hz, 3H).

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with EtOAc (4×1.5 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-2c8a3af4ba304ceaa439199305c18253
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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