4-Methylmorpholine → HCID 15957082, compound

HRID 2377111Notes

Reaction equation

HRID 2377111 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][N:7]2[C:11]3=[CH:12][N:13]=[C:14]([C:16]([OH:18])=O)[CH:15]=[C:10]3[C:9]([CH2:19][O:20][CH2:21][CH2:22][N:23]3[CH2:27][CH2:26][CH2:25][C:24]3=[O:28])=[CH:8]2)=[CH:4][CH:3]=1.ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.Cl.[CH3:50][NH:51][OH:52]>CN(C=O)C>[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][N:7]2[C:11]3=[CH:12][N:13]=[C:14]([C:16]([N:51]([OH:52])[CH3:50])=[O:18])[CH:15]=[C:10]3[C:9]([CH2:19][O:20][CH2:21][CH2:22][N:23]3[CH2:27][CH2:26][CH2:25][C:24]3=[O:28])=[CH:8]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 77906N-methylhydroxylamine hydrochlorideHCID 598558171h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(4-fluorophenyl)methyl]-3-[[2-(2-oxo-1-pyrrolidinyl)ethoxy]methyl]-

Product 1

HCID 15957082HCID 15957082, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 1-(4-fluorobenzyl)-3-{[2-(2-oxopyrrolidin-1-yl)ethoxy]methyl}-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid (0.817 g, 1.99 mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (0.418 g, 2.38 mmol) in DMF (20 mL) was added N-methyl morpholine (0.2409, 2.38 mmol). After stirring at room temperature for 2 hours, N-methyl hydroxylamine hydrochloride (1.66 g, 19.9 mmol) was added. The reaction stirred for 16 hours at room temperature. After stirring for 16 hours, the reaction was concentrated in vacuo yielding a yellow oil. The oily residue was partitioned between a saturated sodium bicarbonate solution and ethyl acetate (50:50, 50 mL: 50 mL). The organic phase was separated and the aqueous phase extracted with ethyl acetate (2×100 mL). The organic phases were combined, washed with brine (100 mL), and dried over Na2SO4. The solution was filtered, concentrated, and triturated with diethyl ether to yield a pale yellow solid. The solid was recrystalized from isopropyl alcohol to give 1-(4-fluorobenzyl)-N-hydroxy-N-methyl-3-{[2-(2-oxopyrrolidin-1-yl)ethoxy]methyl}-1H-pyrrolo[2,3-c]pyridine-5-carboxamide as clear needles (0.425 g, 49% yield). 1H NMR (400 MHz, DMSO-D6) δ ppm 1.76-1.85 (m, 2H) 2.13 (t, J=8.08 Hz, 2H) 3.26-3.35 (m, 8H) 3.51 (t, J=5.43 Hz, 2H) 4.65 (s, 2H) 5.54 (s, 2H) 7.16 (t, J=8.84 Hz, 2H) 7.36 (dd, J=8.59, 5.56 Hz, 2H) 7.86 (s, 1H) 8.01 (s, 1H) 8.89 (s, 1H)

Workup

  1. stirringThe reaction stirred for 16 hours at room temperature
  2. stirringAfter stirring for 16 hours
  3. concentrationthe reaction was concentrated in vacuo
  4. customyielding a yellow oil
  5. customThe oily residue was partitioned between a saturated sodium bicarbonate solution and ethyl acetate (50:50, 50 mL: 50 mL)
  6. customThe organic phase was separated
  7. extractionthe aqueous phase extracted with ethyl acetate (2×100 mL)
  8. washwashed with brine (100 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationThe solution was filtered
  11. concentrationconcentrated
  12. customtriturated with diethyl ether
  13. customto yield a pale yellow solid
  14. customThe solid was recrystalized from isopropyl alcohol

Sources & evidence

ORD record
ord-1bc646f87b534f94a65cf7a78dcf395c
Source dataset
uspto-grants-2008_12
Patent number
US07468375B2

Reaction notes

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