4-Methylmorpholine → HCID 15957077, compound

HRID 2377105Notes

Reaction equation

HRID 2377105 reaction equation
[CH3:1][C:2]1([CH3:30])[O:6][C@H:5]([CH2:7][O:8][CH2:9][C:10]2[C:18]3[C:13](=[CH:14][N:15]=[C:16]([C:19](O)=[O:20])[CH:17]=3)[N:12]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[CH:11]=2)[CH2:4][O:3]1.CN1CCOCC1.Cl.[CH3:39][NH:40][OH:41]>CN(C=O)C.CCOC(C)=O>[CH3:1][C:2]1([CH3:30])[O:6][C@H:5]([CH2:7][O:8][CH2:9][C:10]2[C:18]3[C:13](=[CH:14][N:15]=[C:16]([C:19]([N:40]([OH:41])[CH3:39])=[O:20])[CH:17]=3)[N:12]([CH2:22][C:23]3[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=3)[CH:11]=2)[CH2:4][O:3]1

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 77906N-methylhydroxylamine hydrochlorideHCID 69195471HCID 69195471, compound

Product 1

HCID 15957077HCID 15957077, compoundYield 44.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-({[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}methyl)-1-(4-fluorobenzyl)-1H -pyrrolo[2,3-c]pyridine-5-carboxylic acid (200 mg 0.4828 mmol) in anhydrous DMF (10 mL) was added CDMT (102 mg 0.5793 mmol 1.2 eq.) and NMM (0.064 mL, 0.5793 mmol 1.2 eq.). The mixture, under nitrogen, was stirred for 2 hours, during which it slowly darkened to a deep orange. N-Methylhydroxylamine Hydrochloride (202 mg 2.414 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 prep HPLC to give 95 mg (44%) of 3-({[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy)methyl)-1-(4-fluorobenzyl)-N -hydroxy-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide as a white powder. LC-MS (Eclipse XDB-C8, 0.8 mL/min, gradient 80:20 to 5:95H2O (+0.1% HOAc):CH3CN—5 minutes, ESI, +mode): RT—2.278 min, m/e=444.2 (M+H+, base). 1H-NMR (400 MHz, CDCl3): δ=1.34 (s, 3H), 1.38 (s, 3H), 3.52 (m, 4H), 3.62 (m, 1H), 3.67 (m, 1H), 4.04 (m, 1H), 4.32 (m, 1H) 4.77 (q, 2H), 5.38 (s, 2H), 7.06 (m, 2H), 7.16 (m, 2H), 7.43 (s, 1H), 8.47 (s, 1H), 8.64 (s, 1H).

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 prep HPLC

Sources & evidence

ORD record
ord-86650695d5f24ab08d9797fec677ee1d
Source dataset
uspto-grants-2008_12
Patent number
US07468375B2

Reaction notes

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