Aluminium lithium hydride → 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [5-hydroxymethyl-1-(6-methoxy-3,4-dihydro-2H-1-thia-9-aza-phenanthren-3-ylmethyl)-pyrrolidin-3-yl]-amide

HRID 633833Notes

Reaction equation

HRID 633833 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C[O:8][C:9]([CH:11]1[CH2:15][CH:14]([NH:16][C:17]([C:19]2[CH:20]=[CH:21][C:22]3[S:27][CH2:26][C:25](=[O:28])[NH:24][C:23]=3[CH:29]=2)=[O:18])[CH2:13][N:12]1[CH2:30][CH:31]1[CH2:44][C:43]2[C:42]3[C:37](=[CH:38][CH:39]=[C:40]([O:45][CH3:46])[CH:41]=3)[N:36]=[CH:35][C:34]=2[S:33][CH2:32]1)=O>O1CCCC1>[OH:8][CH2:9][CH:11]1[N:12]([CH2:30][CH:31]2[CH2:44][C:43]3[C:42]4[C:37](=[CH:38][CH:39]=[C:40]([O:45][CH3:46])[CH:41]=4)[N:36]=[CH:35][C:34]=3[S:33][CH2:32]2)[CH2:13][CH:14]([NH:16][C:17]([C:19]2[CH:20]=[CH:21][C:22]3[S:27][CH2:26][C:25](=[O:28])[NH:24][C:23]=3[CH:29]=2)=[O:18])[CH2:15]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 711188941-(6-methoxy-3,4-dihydro-2H-1-thia-9-aza-phenanthren-3-ylmethyl)-4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)-amino]-pyrrolidine-2-carboxylic acid methyl ester

Product 1

HCID 714755273-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [5-hydroxymethyl-1-(6-methoxy-3,4-dihydro-2H-1-thia-9-aza-phenanthren-3-ylmethyl)-pyrrolidin-3-yl]-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium aluminium hydride (2.0 M solution in tetrahydrofuran, 85 μL, 0.17 mmol, 1.1 eq) is cautiously added at room temperature to a stirred solution of 1-(6-methoxy-3,4-dihydro-2H-1-thia-9-aza-phenanthren-3-ylmethyl)-4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)-amino]-pyrrolidine-2-carboxylic acid methyl ester (110 mg, 0.15 mmol, 1.0 eq) in tetrahydrofuran (5 mL). After 1 hour stirring at room temperature, the reaction mixture is cautiously quenched with ice-water (5 mL) and extracted with dichloromethane (3×10 mL) and water (10 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a crude product that is purified by preparative HPLC to afford 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [5-hydroxymethyl-1-(6-methoxy-3,4-dihydro-2H-1-thia-9-aza-phenanthren-3-ylmethyl)-pyrrolidin-3-yl]-amide as an off-white lyophilized powder (14 mg, 16% yield).

Workup

  1. customthe reaction mixture is cautiously quenched with ice-water (5 mL)
  2. extractionextracted with dichloromethane (3×10 mL) and water (10 mL)
  3. dry with materialThe combined organic layers are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude product that
  7. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-02396a54ef24485b865a81757452e4d3
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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