Hydrochloric Acid → N-(trans-4-Fluoropyrrolidin-3-yl)-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4 (5H)-yl)quinazolin-4-amine

HRID 540260Notes

Reaction equation

HRID 540260 reaction equation
[F:1][C@H:2]1[C@H:6]([NH:7][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([CH3:18])[CH:16]=3)[N:11]=[C:10]([N:19]3[CH2:25][C:24]4[CH:26]=[CH:27][CH:28]=[CH:29][C:23]=4[S:22](=[O:30])[CH2:21][CH2:20]3)[N:9]=2)[CH2:5][N:4](C(OCC2C=CC=CC=2)=O)[CH2:3]1.Cl.[OH-].[Na+]>>[F:1][C@@H:2]1[CH2:3][NH:4][CH2:5][C@H:6]1[NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH3:18])[CH:16]=2)[N:11]=[C:10]([N:19]2[CH2:25][C:24]3[CH:26]=[CH:27][CH:28]=[CH:29][C:23]=3[S:22](=[O:30])[CH2:21][CH2:20]2)[N:9]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86691426benzyl trans-3-fluoro-4-{[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-yl]amino}pyrrolidine-1-carboxylate

Product 1

HCID 86691427N-(trans-4-Fluoropyrrolidin-3-yl)-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4 (5H)-yl)quinazolin-4-amine

Procedure

A mixture of benzyl trans-3-fluoro-4-{[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-yl]amino}pyrrolidine-1-carboxylate (200 mg, 0.35 mmol) and an aqueous solution of hydrochloric acid (5 mL, 6 N) was refluxed for 6 hours. The resulting mixture was basified by adding an aqueous solution of sodium hydroxide (1 N) to pH 10, and then extracted with dichloromethane (50 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by preparative HPLC to afford the desired compound as a yellow solid. MS obsd. (ESI+) [(M+H)+] 426, 1H NMR (400 MHz, CD3OD) δ ppm 7.76 (m, 3 H), 7.45 (m, 4 H), 5.32 (m, 3 H), 4.61 (s, 3 H), 3.70-3.11 (m, 6 H), 2.41 (s, 3 H).

Workup

  1. extractionextracted with dichloromethane (50 mL)
  2. washThe organic layer was washed with brine
  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-32414f28dc11476d92ef9b077892a585
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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