4-Methylmorpholine → HCID 24760641, compound

HRID 639532Notes

Reaction equation

HRID 639532 reaction equation
C(O[C:4]([C:6]1[N:7]=[CH:8][C:9]([F:15])=[C:10]2[CH:14]=[CH:13][NH:12][C:11]=12)=[O:5])C.[OH-].[K+].[C:18]([C:22]1[CH:42]=[CH:41][C:25]([CH2:26][NH:27][CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([C:37]([F:40])([F:39])[F:38])[CH:31]=2)=[CH:24][CH:23]=1)([CH3:21])([CH3:20])[CH3:19].CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[C:18]([C:22]1[CH:42]=[CH:41][C:25]([CH2:26][N:27]([CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[C:32]([C:37]([F:39])([F:40])[F:38])[CH:31]=2)[C:4]([C:6]2[N:7]=[CH:8][C:9]([F:15])=[C:10]3[CH:14]=[CH:13][NH:12][C:11]=23)=[O:5])=[CH:24][CH:23]=1)([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 14797Potassium HydroxideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68576716HCID 68576716, compoundHCID 68579087HCID 68579087, compound

Product 1

HCID 24760641HCID 24760641, compoundYield 74.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-fluoro-1H-pyrrolo[2,3-c]pyridine-7-carboxylic acid ethyl ester (50 mg, 0.24 mmol) in THF (0.7 mL) was treated with 2 M aq. potassium hydroxide solution (0.24 mL, 0.48 mmol) and stirred for 90 min at RT. The reaction mixture was then evaporated, the residue dissolved in DMF (3.2 mL) and treated with (4-tert-butyl-benzyl)-[2-(4-chloro-3-trifluoromethyl-phenyl)-ethyl]-amine (98 mg, 0.26 mmol), N-methylmorpholine (73 mg, 0.72 mmol), and HBTU (137 mg, 0.36 mmol). After 16 h, the reaction mixture was partitioned between water and ethyl acetate, the organic layer was washed with brine, dried (MgSO4), and evaporated. Chromatography of the residue (SiO2, heptane/ethyl acetate 97:3) afforded the title compound (95 mg, 74%). White foam, MS (ISP) 532.3 (M+H)+.

Workup

  1. customThe reaction mixture was then evaporated
  2. dissolutionthe residue dissolved in DMF (3.2 mL)
  3. waitAfter 16 h
  4. customthe reaction mixture was partitioned between water and ethyl acetate
  5. washthe organic layer was washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated

Sources & evidence

ORD record
ord-75cc8eab17de46f8bc11716e7c1c12fe
Source dataset
uspto-grants-2010_04
Patent number
US07691876B2

Reaction notes

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