Hydrochloric Acid → Jtj4sgm9LN

HRID 78743Notes

Reaction equation

HRID 78743 reaction equation
[ClH:1].[N:2]1([C:11](=[O:34])/[CH:12]=[CH:13]/[C@@H:14]([NH:17][C:18]([C:20]2([NH:26]C(=O)OC(C)(C)C)[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[O:19])[CH2:15][CH3:16])[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].[NH2:26][C:20]1([C:18]([NH:17][C@@H:14]([CH2:15][CH3:16])/[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:34])=[O:19])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86704316(S,E)-tert-butyl (4-((6-(indolin-1-yl)-6-oxohex-4-en-3-yl)carbamoyl)tetrahydro-2H-pyran-4-yl)carbamate

Product 1

HCID 74766536Jtj4sgm9LNYield 89.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
65 °C

Procedure

A solution of concentrated aq. HCl (0.23 mL, 2.76 mmol) was added to a solution of 1,1-dimethylethyl [4-({[(1S,2E)-4-(2,3-dihydro-1H-indol-1-yl)-1-ethyl-4-oxo-2-buten-1-yl]amino}carbonyl)tetrahydro-2H-pyran-4-yl]carbamate (251 mg, 0.549 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) for 1 h 45 min. The solvent was evaporated under reduced pressure. 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 193.3 mg (89%) of the title compound. LC-MS m/z 358 (M+H)+, 0.68 (ret time). 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.14 (br. s., 1H); 7.25 (d, J=7.03 Hz, 1H); 7.18 (t, J=7.53 Hz, 1H); 7.02-7.09 (m, 1H); 6.83 (dd, J=15.18, 6.65 Hz, 1H); 6.49 (d, J=14.8 Hz, 1H); 4.56 (d, J=7.28 Hz, 1H); 4.22 (br. s., 2H); 3.95 (d, J=7.53 Hz, 1H); 3.88-3.94 (m, 1H); 3.71-3.78 (m, 2H); 3.23 (br. s., 2H); 2.39-2.46 (m, 2H); 1.79-1.86 (m, 2H); 1.75 (s, 1H); 1.72 (d, J=8.28 Hz, 1H); 1.00 (t, J=7.40 Hz, 3H).

Workup

  1. customThe reaction flask was fitted with an air condenser
  2. customThe solvent was evaporated under reduced pressure
  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-3be792d50a714983baa12021848093c1
Source dataset
uspto-grants-2014_09
Patent number
US08841463B2

Reaction notes

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