Hydrochloric Acid → (S,E)-4-Amino-N-(1-(indolin-1-yl)-6-methyl-1-oxohept-2-en-4-yl)tetrahydro-2H-pyran-4-carboxamide hydrochloride

HRID 78744Notes

Reaction equation

HRID 78744 reaction equation
[ClH:1].[N:2]1([C:11](=[O:36])/[CH:12]=[CH:13]/[C@@H:14]([NH:19][C:20]([C:22]2([NH:28]C(=O)OC(C)(C)C)[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[O:21])[CH2:15][CH:16]([CH3:18])[CH3:17])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1>C(O)(C)C>[ClH:1].[NH2:28][C:22]1([C:20]([NH:19][C@@H:14]([CH2:15][CH:16]([CH3:18])[CH3:17])/[CH:13]=[CH:12]/[C:11]([N:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH2:4][CH2:3]2)=[O:36])=[O:21])[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 867043181,1-dimethylethyl [4-({[(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-(2-methylpropyl)-4-oxo-2-buten-1-yl]amino}carbonyl)tetrahydro-2H-pyran-4-yl]carbamate

Product 1

HCID 86704319(S,E)-4-Amino-N-(1-(indolin-1-yl)-6-methyl-1-oxohept-2-en-4-yl)tetrahydro-2H-pyran-4-carboxamide hydrochlorideYield 60%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
65 °C

Procedure

A solution of concentrated aq. HCl (0.22 mL, 2.64 mmol) was added to a solution of 1,1-dimethylethyl [4-({[(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-(2-methylpropyl)-4-oxo-2-buten-1-yl]amino}carbonyl)tetrahydro-2H-pyran-4-yl]carbamate (251 mg, 0.517 mmol) in isopropanol (2.5 mL). The reaction flask was fitted with an air condenser, and the reaction mixture was heated to 65° C. (bath temp). After 1 h 45 min, the solvent was evaporated under reduced pressure at 60° C. Water (5 mL) was added to the residue, and the mixture was concentrated under reduced pressure at 65° C. Water (2 mL) was added to the residue, and the mixture was lyophilized, giving 130.6 mg (60%) of the title compound. LC-MS m/z 386 (M+H)+, 0.79 (ret time). 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.15 (d, J=7.03 Hz, 1H); 7.25 (d, J=7.03 Hz, 1H); 7.18 (t, J=7.65 Hz, 1H); 7.06 (t, J=7.91 Hz, 1H); 6.81 (dd, J=15.18, 6.40 Hz, 1H); 6.49 (br. s., 1H); 4.73-4.85 (m, 2H); 4.21 (t, J=8.28 Hz, 2H); 3.91-3.97 (m, 2H); 3.70-3.77 (m, 2H); 3.25-3.21 (m, 2H); 2.35-2.48 (m, 2H); 1.82 (d, J=14.31 Hz, 2H); 1.63-1.71 (m, 2H); 1.50-1.57 (m, 1H); 0.98 (dd, J=11.92, 6.40 Hz, 6H).

Workup

  1. customThe reaction flask was fitted with an air condenser
  2. customthe solvent was evaporated under reduced pressure at 60° C
  3. additionWater (5 mL) was added to the residue
  4. concentrationthe mixture was concentrated under reduced pressure at 65° C
  5. additionWater (2 mL) was added to the residue

Sources & evidence

ORD record
ord-4224242f475f4684aae5e6f21f382479
Source dataset
uspto-grants-2014_09
Patent number
US08841463B2

Reaction notes

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