4-Methylmorpholine → HCID 22050802, compound

HRID 1832071Notes

Reaction equation

HRID 1832071 reaction equation
[Br:1][C:2]1[C:3](=[O:29])[N:4]([CH2:19][C:20]2[CH:28]=[CH:27][C:23]([C:24](O)=[O:25])=[CH:22][N:21]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].ON1C2C=CC=CC=2N=N1.[CH3:40][N:41]1CC[O:44][CH2:43][CH2:42]1.Cl.CN(C)CCCN=C=NCC.CNCCO>CN(C)C=O.O>[Br:1][C:2]1[C:3](=[O:29])[N:4]([CH2:19][C:20]2[CH:28]=[CH:27][C:23]([C:24]([N:41]([CH2:42][CH2:43][OH:44])[CH3:40])=[O:25])=[CH:22][N:21]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 80162-(Methylamino)ethanolHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22050152HCID 22050152, compound

Product 1

HCID 22050802HCID 22050802, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

6-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]methyl}nicotinic acid (from step 2)(230 mg, 0.5 mmol) was added into the 1-hydroxybenzotriazole (101 mg, 0.75 mmol) in 5 ml of N,N-dimethylforamide. 4-methyl morpholine (0.16 ml, 1.5 mmol) was added into the mixture followed by addition of 1-(3-(dimethylamino) propyl-3-ethylcarbodiimide hydrochloride (143 mg, 0.75 mmol). Stirred the mixture for 30 minute to become homogenous solution. To that homogenous solution, was added 2-(methylamino) ethanol (0.06 ml, 0.75 mmol) and the mixture was stirred for 20 hours. Water (150 ml) was added into the reaction mixture and the product was extracted using ethyl acetate (400 ml×2). The combined ethyl acetate solution was dried over anhydrous magnesium sulfate and evaporated to dryness. 1H NMR (400 MHz, DMSO-d6) δ 8.47 (app br s, 1H), 7.80 (br d, J=7.92 Hz, 1H), 7.64 (app q, J=6.58 Hz, 1H), 7.30 (m, 2H), 7.15 (m, 1H), 6.56 (s, 1H), 5.39 (s, 2H), 5.28 (s, 2H), 3.46 (m, 2H), 3.23 (m, 2H), 2.93 (m, 3H), 2.36 (s, 3H); LC/MS, tr=2.29 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-HRMS m/z 522.0850 (M+H calcd for C23H23BrF2N3O4 requires 522.0835).

Workup

  1. stirringthe mixture was stirred for 20 hours
  2. extractionthe product was extracted
  3. dry with materialThe combined ethyl acetate solution was dried over anhydrous magnesium sulfate
  4. customevaporated to dryness
  5. customLC/MS, tr=2.29 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.)

Sources & evidence

ORD record
ord-addd35e83e71421f91b8413e064e776f
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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