Hydrochloric Acid → 3-{[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]amino}propane-1,2-diol

HRID 540253Notes

Reaction equation

HRID 540253 reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][CH2:13][CH:14]2[CH2:18][O:17]C(C)(C)[O:15]2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:21])[CH:8]=2)[N:3]=1.C(N(CC)CC)C.[S:29]1(=[O:41])(=[O:40])[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[CH2:33][NH:32][CH2:31][CH2:30]1.Cl>CN(C)C=O.CO>[O:41]=[S:29]1(=[O:40])[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[CH2:33][N:32]([C:2]2[N:11]=[C:10]([NH:12][CH2:13][CH:14]([OH:15])[CH2:18][OH:17])[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([CH3:21])[CH:8]=3)[N:3]=2)[CH2:31][CH2:30]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 196081962,3,4,5-Tetrahydrobenzo[F][1,4]thiazepine 1,1-dioxideHCID 866914222-Chloro-N-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-6-methylquinazolin-4-amine

Product 1

HCID 712621393-{[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]amino}propane-1,2-diolYield 10%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-chloro-N-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-6-methylquinazolin-4-amine (431.2 mg, 1.4 mmol) and triethylamine (0.8 mL), 2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (296.1 mg, 1.5 mmol) in N,N-dimethyl-formamide (1.0 mL) was stirred at 160° C. for 4 hours. After being cooled to room temperature, the reaction mixture was dissolved in methanol (2.0 mL). To the above mixture, concentrated hydrochloric acid (0.5 mL) was added, and the resulting mixture was stirred at room temperature for 1 hour, and then extracted with ethyl acetate (100 mL). The organic layer was washed with brine (50 mL×2), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by preparative HPLC to afford 59.2 mg of the product as a white solid (yield was 10%). MS obsd. (ESI+) [(M+H)+] 429, 1H NMR (400 MHz, CD3OD) δ ppm 7.98 (dd, J=7.83, 1.01 Hz, 1 H), 7.90 (d, J=7.58 Hz, 1 H), 7.66-7.55 (m, 2 H), 7.50-7.35 (m, 2 H), 7.35-7.28 (m, 1 H), 5.21 (brs, 2 H), 4.56 (brs, 2 H), 4.05-3.95 (m, 1 H), 3.86 (dd, J=13.26, 4.42 Hz, 1 H), 3.73-3.56 (m, 3 H), 3.53 (t, J=5.05 Hz, 2 H), 2.39 (s, 3 H).

Workup

  1. extractionextracted with ethyl acetate (100 mL)
  2. washThe organic layer was washed with brine (50 mL×2)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-7dc4b41ce797419c9dbff53c6e41b3de
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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