4-Methylmorpholine → HCID 15957087, compound

HRID 2377118Notes

Reaction equation

HRID 2377118 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[C:11]3=[CH:12][N:13]=[C:14]([C:16](O)=[O:17])[CH:15]=[C:10]3[C:9]([CH2:19][O:20][CH3:21])=[CH:8]2)=[CH:4][CH:3]=1.CN1CCOCC1.Cl.[CH3:32][NH:33][OH:34]>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[C:11]3=[CH:12][N:13]=[C:14]([C:16]([N:33]([OH:34])[CH3:32])=[O:17])[CH:15]=[C:10]3[C:9]([CH2:19][O:20][CH3:21])=[CH:8]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 77906N-methylhydroxylamine hydrochlorideHCID 59855807HCID 59855807, compound

Product 1

HCID 15957087HCID 15957087, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
4 °C

Procedure

To a solution of 1-(4-fluorobenzyl)-3-(methoxymethyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid 332 mg 0.9467 mmol) in anhydrous DMF (8.0 mL) was added CDMT (200 mg 1.136 mmol 1.2 eq.) and NMM (N-methyl morpholine) (0.13 mL 1.136 mmol 1.2 eq.). The mixture, under nitrogen, was stirred for 2.0 hours, during which it slowly darkened to a deep orange. N-Methylhydroxylamine hydrochloride (395 mg 4.734 mmol 5.0 eq) was added and stirring continued for 10 hours. The reaction was judged to be complete by HPLC-MS analysis and the volatiles were removed in vacuo (ca. 2 torr) to give a golden yellow oil. This oil was dissolved in EtOAc (30 mL) and washed with water (3×20 mL) and brine (20 mL). The organic phase was separated, dried (Na2SO4), and concentrated in vacuo to afford the crude product which was purified by recrystallisation in hot IPA (20 ml) with cooling at 4° C. overnight to give 194 mg (60%) of 1-(4-fluorobenzyl)-N-hydroxy-3-(methoxymethyl)-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide as a white solid. LC-MS (Eclipse XDB-C8, 0.8 mL/min, gradient 80:20 to 5:95H2O (+0.1% HOAc):CH3CN—3 minutes, APCI, +mode): RT—1.028 min, m/e=344.2 (M+H+, base). 1H-NMR (300 MHz, DMSO): δ =3.26 (s, 3H), 3.34 (s, 3H), 4.57 (s, 2H), 5.54 (s, 2H), 7.14 (t, 2H), 7.36 (m, 2H), 7.87 (s, 1H), 8.02 (s, 1H), 8.92 (s, 1H). Found: C, 62.72; H, 5.20; N, 12.17%. C18H18FN3O3, requires C, 62.97; H, 5.28; N, 12.24%.

Workup

  1. stirringstirring
  2. waitcontinued for 10 hours
  3. customthe volatiles were removed in vacuo (ca. 2 torr)
  4. customto give a golden yellow oil
  5. washwashed with water (3×20 mL) and brine (20 mL)
  6. customThe organic phase was separated
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customto afford the crude product which
  10. customwas purified by recrystallisation in hot IPA (20 ml)

Sources & evidence

ORD record
ord-52294c1c085e44719f1f0899dc360c4a
Source dataset
uspto-grants-2008_12
Patent number
US07468375B2

Reaction notes

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