Hydrochloric Acid → HCID 44252022, compound

HRID 19023Notes

Reaction equation

HRID 19023 reaction equation
[CH:1]1([CH2:6][C@H:7]([N:24]2[CH2:28][C:27]([O:29][C:30]3[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:31]=3[F:37])=[CH:26][C:25]2=[O:38])[C:8]([NH:10][C:11]2[CH:15]=[CH:14][N:13]([CH2:16][C@@H:17]3[CH2:21][O:20]C(C)(C)[O:18]3)[N:12]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl>O1CCCC1.C(OCC)(=O)C>[CH:1]1([CH2:6][C@H:7]([N:24]2[CH2:28][C:27]([O:29][C:30]3[C:35]([F:36])=[CH:34][CH:33]=[CH:32][C:31]=3[F:37])=[CH:26][C:25]2=[O:38])[C:8]([NH:10][C:11]2[CH:15]=[CH:14][N:13]([CH2:16][C@@H:17]([OH:18])[CH2:21][OH:20])[N:12]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 57920150HCID 57920150, compound

Product 1

HCID 44252022HCID 44252022, compoundYield 64.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of (S)-3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-propionamide (prepared as in Example 87, 120 mg, 0.22 mmol) in tetrahydrofuran (20 mL) was treated with 2N aqueous hydrochloric acid (10 mL). The reaction mixture was stirred for 4 h at 25° C. The reaction mixture was adjusted to neutral and diluted with ethyl acetate, washed with water, a saturated sodium chloride solution and dried over sodium sulfate. The organic layer was concentrated to afford (S)-3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-propionamide (70 mg, 63%) as an off-white solid: HR-ES-MS m/z calculated for C24H28F2N4O5 [M+H]+ 491.2101, observed 491.2102; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.08 (br. s., 1H) 1.28 (br. s., 1H) 1.36-1.95 (m, 9H) 3.19-3.30 (m, 2H) 3.64-3.80 (m, 1H) 3.80-3.91 (m, 1H) 4.07 (dd, J=13.6, 3.9 Hz, 1H) 4.28 (d, J=18.7 Hz, 1H) 4.61 (d, J=18.7 Hz, 1H) 4.69 (t, J=5.6 Hz, 1H) 4.79 (dd, J=10.3, 4.8 Hz, 1H) 4.92 (d, J=5.4 Hz, 1H) 5.01 (s, 1H) 6.39 (d, J=2.1 Hz, 1H) 7.22-7.48 (m, 3H) 7.51 (d, J=2.1 Hz, 1H) 10.78 (s, 1H).

Workup

  1. washwashed with water
  2. dry with materiala saturated sodium chloride solution and dried over sodium sulfate
  3. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-5b05d427dc644f6380f2fe5f22a20b23
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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