Hydrochloric Acid → N~1~-[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4,4,4-trifluorobutane-1,3-diamine

HRID 540174Notes

Reaction equation

HRID 540174 reaction equation
[NH2:1][CH:2]([C:31]([F:34])([F:33])[F:32])[CH2:3][C:4]([NH:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH3:17])[CH:15]=2)[N:10]=[C:9]([N:18]2[CH2:24][C:23]3[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=3[S:21](=[O:30])(=[O:29])[CH2:20][CH2:19]2)[CH:8]=1)=O.Cl>CSC>[O:30]=[S:21]1(=[O:29])[C:22]2[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=2[CH2:24][N:18]([C:9]2[CH:8]=[C:7]([NH:6][CH2:4][CH2:3][CH:2]([NH2:1])[C:31]([F:34])([F:33])[F:32])[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([CH3:17])[CH:15]=3)[N:10]=2)[CH2:19][CH2:20]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 712554253-Amino-N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4,4,4-trifluorobutanamide

Product 1

HCID 71262110N~1~-[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4,4,4-trifluorobutane-1,3-diamineYield 65%

Reagents, catalysts & solvents 1

HCID 1068Dimethyl SulfideSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 3-amino-N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4,4,4-trifluorobutanamide (120 mg, 0.245 mmol) was added a solution of borane-methyl sulfide complex in methyl sulfide (5 M, 1.0 mL). The resulting solution was heated at 85° C. for 2 hours. After being cooled to room temperature, the mixture was acidified by careful addition of an aqueous solution of hydrochloric acid (1 M) to about pH 4, and then stirred at room temperature overnight. The resulting mixture was concentrated in vacuo. The residue was neutralized with a 10% aqueous solution of sodium hydroxide to pH >9, and then extracted with dichloromethane (20 mL×3). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography to afford 60 mg of the title product as a solid (yield was 65%). MS obsd. (ESI+) [(M+H)+] 479, 1H NMR (400 MHz, CDCl3) δ ppm 8.04 (d, J=7.6 Hz, 1 H), 7.65 (d, J=7.6 Hz, 1 H), 7.50-7.49 (m, 2 H), 7.38 (t, J=7.2 Hz, 1 H), 7.30 (m, 1 H), 6.06 (s, 1 H), 5.93 (s, 1 H), 5.12 (s, 1 H), 3.63 (m, 3 H), 4.62 (brs, 2 H), 3.45 (m, 1 H), 3.33 (m, 1 H), 2.42 (s, 3 H), 2.22 (m, 1 H), 2.03 (s, 1 H), 1.82 (m, 1 H).

Workup

  1. temperatureAfter being cooled to room temperature
  2. concentrationThe resulting mixture was concentrated in vacuo
  3. extractionextracted with dichloromethane (20 mL×3)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-e2f9d86ff2934eda9f9fcabb6d405e82
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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