Morpholine → HCID 21099114, compound

HRID 1351737Notes

Reaction equation

HRID 1351737 reaction equation
[C:1]([Si:5]([CH3:30])([CH3:29])[O:6][CH2:7][CH2:8][C:9]1([CH2:26][CH2:27][CH3:28])[C:14]2[NH:15][C:16]3[C:17]([F:25])=[CH:18][CH:19]=[C:20]([C:22]([OH:24])=O)[C:21]=3[C:13]=2[CH2:12][CH2:11][O:10]1)([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.[NH:61]1[CH2:66][CH2:65][O:64][CH2:63][CH2:62]1>CN(C=O)C.O>[C:1]([Si:5]([CH3:29])([CH3:30])[O:6][CH2:7][CH2:8][C:9]1([CH2:26][CH2:27][CH3:28])[C:14]2[NH:15][C:16]3[C:21]([C:13]=2[CH2:12][CH2:11][O:10]1)=[C:20]([C:22]([N:61]1[CH2:66][CH2:65][O:64][CH2:63][CH2:62]1)=[O:24])[CH:19]=[CH:18][C:17]=3[F:25])([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 5

HCID 8083MorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 21099115HCID 21099115, compound

Product 1

HCID 21099114HCID 21099114, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-8-fluoro-1-propyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indole-5-carboxylic acid (6) (400 mg, 0.918 mmol), EDCI (211 mg, 1.10 mmol) and HOBt (186 mg, 1.38 mmol) in DMF ( 5 mL) was added diisopropylethylamine (0.80 mL, 4.59 mmol) at room temperature. Morpholine (0.12 mL, 1.38 mmol) was added to the mixture and the mixture was stirred overnight at room temperature. The solution was diluted with H2O (10 mL) and extracted with EtOAc (3×15 mL). The organic solution was brine washed (30 mL), dried (Na2SO4) and concentrated. The residue was purified by flash chromatography (silica, 50% EtOAc in hexanes) to give 415 mg (90%) of title compound as a colorless oil. 1H NMR (CDCl3): 300 MHz δ 9.38 (s, 1H), 6.77 (m, 2H), 3.86–3.20 (m, 12 H), 2.67 (m, 2H), 1.97–1.15 (m, 6H), 0.81 (s, 9H), 0.76 (t, J=7.34 Hz, 3H), 0.06 (s, 3H), 0.03 (s, 3H).

Workup

  1. extractionextracted with EtOAc (3×15 mL)
  2. washwashed (30 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (silica, 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-61f3b02941bb44d29b7f5e55c23d3dbe
Source dataset
uspto-grants-2007_05
Patent number
US07217730B2

Reaction notes

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