Morpholine → HCID 71475524, compound

HRID 633814Notes

Reaction equation

HRID 633814 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH3:7][O:8][C:9]1[CH:10]=[C:11]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][C:17]1[O:16][CH2:15][CH:14]([CH2:23][N:24]3[CH2:28][CH:27]([NH:29][C:30]([C:32]4[CH:33]=[CH:34][C:35]5[S:40][CH2:39][C:38](=[O:41])[NH:37][C:36]=5[CH:42]=4)=[O:31])[CH2:26][CH:25]3[C:43](O)=[O:44])[CH2:13][C:12]2=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH3:7][O:8][C:9]1[CH:10]=[C:11]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][C:17]1[O:16][CH2:15][CH:14]([CH2:23][N:24]3[CH:25]([C:43]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)=[O:44])[CH2:26][CH:27]([NH:29][C:30]([C:32]4[CH:33]=[CH:34][C:35]5[S:40][CH2:39][C:38](=[O:41])[NH:37][C:36]=5[CH:42]=4)=[O:31])[CH2:28]3)[CH2:13][C:12]2=1

Participants

7

Reactant 5

HCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 71119261HCID 71119261, compound

Product 1

HCID 71475524HCID 71475524, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Morpholine (2 μL, 0.024 mmol, 1.0 eq) is added at room temperature to a stirred solution of 1-(6-methoxy-3,4-dihydro-2H-1-oxa-9-aza-phenanthren-3-ylmethyl)-4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)-amino]-pyrrolidine-2-carboxylic acid (14 mg, 0.024 mmol, 1.0 eq) in N,N-dimethylformamide (2 mL), followed by 1-hydroxybenzotriazole (4 mg, 0.027 mmol, 1.1 eq), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (5 mg, 0.028 mmol, 1.15 eq) and N,N-diisopropylethylamine (13 μL, 0.073 mmol, 3.0 eq). After 15 hours stirring at room temperature, solvent is evaporated and the residue is extracted with dichloromethane (3×5 mL) and water (5 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 [1-(6-methoxy-3,4-dihydro-2H-1-oxa-9-aza-phenanthren-3-ylmethyl)-5-(morpholine-4-carbonyl)-pyrrolidin-3-yl]-amide as a white lyophilized powder (12 mg, 76% yield).

Workup

  1. customsolvent is evaporated
  2. extractionthe residue is extracted with dichloromethane (3×5 mL) and water (5 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-d38af774d593496399e224bca2e098bc
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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