Hydrochloric Acid → HCID 71262232, compound

HRID 540158Notes

Reaction equation

HRID 540158 reaction equation
[NH2:1][CH2:2][CH:3]([OH:30])[CH2:4][NH:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH3:16])[CH:14]=2)[N:9]=[C:8]([N:17]2[CH2:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[S:20](=[O:29])(=[O:28])[CH2:19][CH2:18]2)[CH:7]=1.C([O-])(=O)C.[K+].[N:36]#[C:37]Br.Cl>O.CO>[NH2:36][C:37]1[O:30][CH:3]([CH2:4][NH:5][C:6]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([CH3:16])[CH:14]=3)[N:9]=[C:8]([N:17]3[CH2:23][C:22]4[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=4[S:20](=[O:29])(=[O:28])[CH2:19][CH2:18]3)[CH:7]=2)[CH2:2][N:1]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10476Cyanogen BromideHCID 517044Potassium AcetateHCID 71255314HCID 71255314, compound

Product 1

HCID 71262232HCID 71262232, compoundYield 39.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A mixture of 1-amino-3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propan-2-ol (80 mg, 0.18 mmol, prepared in analogy to Example 9-7) and potassium acetate (89 mg, 0.91 mmol) in a mixture solution of methanol and water (7 ml, V/V=6/1) was added cyanogen bromide (89 mg, 0.84 mmol) at 0° C. After being stirred at room temperature for 3 hours, the mixture was stirred further with concentrated hydrochloric acid (3 mL) for 1 hour, and then concentrated in vacuo. The residue was dissolved in a saturated aqueous solution of sodium bicarbonate (10 mL) and extracted with dichloromethane (15 mL×3). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash column (10% methanol in dichloromethane) to afford 32 mg of the desired product as a white solid. MS obsd. (ESI+) [(M+H)+] 452, 1H NMR (400 MHz, DMSO-d6) δ ppm 7.92-7.87 (m, J=4.6 Hz, 2 H), 7.72 (s, 1 H), 7.65-7.62 (t, J=3.7 Hz, 1 H), 7.49-7.45 (t, J=3.9 Hz, 1 H), 7.32 (d, J=2.1 Hz, 1 H), 7.23 (d, J=2.1 Hz, 1 H), 6.85 (t, J=2.6 Hz, 1 H), 6.46 (brs, 2 H), 6.10 (s, 1 H), 5.10 (s, 2 H), 4.82-4.77 (m, J=4.8 Hz, 1 H), 4.49 (brs, 2 H), 3.75 (m, 1 H), 3.63 (s, 2 H), 3.52 (m, 3 H), 2.35 (s, 3 H).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in a saturated aqueous solution of sodium bicarbonate (10 mL)
  3. extractionextracted with dichloromethane (15 mL×3)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column (10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-9c63a5d25e164cd394f9ea5f4a3be5d8
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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