Cyanogen Bromide → HCID 71262375, compound

HRID 540159Notes

Reaction equation

HRID 540159 reaction equation
[NH2:1][CH2:2][C:3]([CH3:31])([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:37]#[C:38]Br>CO.O>[NH2:37][C:38]1[O:30][C: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)([CH3:31])[CH2:2][N:1]=1

Participants

6

Reactant 3

HCID 10476Cyanogen BromideHCID 517044Potassium AcetateHCID 71254579HCID 71254579, compound

Product 1

HCID 71262375HCID 71262375, compoundYield 38.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 1-amino-3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}-2-methylpropan-2-ol (200 mg, 0.45 mmol, prepared in analogy to Example 11-4) and potassium acetate (240 mg, 2.4 mmol) in methanol (8 mL) and water (2 mL) which was cooled to 0° C., a cooled solution of cyanogen bromide (52.3 mg, 0.5 mmol) in methanol (2 mL) was added. After being stirred at room temperature for 4 hours, the reaction mixture was concentrated in vacuo. The residue was diluted with ethyl acetate (50 mL), washed with water (50 mL), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography on silica gel to give 80 mg of the product as a white powder. MS obsd. (ESI+) [(M+H)+] 466, 1H NMR (400 MHz, CD3OD) δ ppm 7.95 (d, J=7.6 Hz, 1 H), 7.83 (d, J=7.2 Hz, 1 H), 7.60 (m, 2 H), 7.46-7.39 (m, 2 H), 7.29 (dd, J=1.6, 8.8 Hz, 1 H), 6.19 (s, 1 H), 5.18-5.09 (m, 2 H), 4.51 (brs, 2 H), 3.82 (d, J=11.2 Hz, 1 H), 3.65 (s, 2 H), 2.57 (m, 3 H), 2.41 (s, 3 H), 1.62 (s, 3 H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. additionThe residue was diluted with ethyl acetate (50 mL)
  3. washwashed with water (50 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-af57aced38a64cad87420756acfbf82c
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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