4-Methylmorpholine → (S)-2-{4-[(4-Cyano-pyridine-2-carbonyl)-amino]-3-fluoro-phenyl}-morpholine-4-carboxylic acid tert-butyl ester

HRID 571846Notes

Reaction equation

HRID 571846 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[C:16]([F:21])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:22]([C:24]1[CH:29]=[CH:28][N:27]=[C:26]([C:30](O)=[O:31])[CH:25]=1)#[N:23].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:30]([C:26]3[CH:25]=[C:24]([C:22]#[N:23])[CH:29]=[CH:28][N:27]=3)=[O:31])=[C:16]([F:21])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 242137694-Cyanopyridine-2-carboxylic acidHCID 68325451(S)-tert-Butyl 2-(4-amino-3-fluorophenyl)morpholine-4-carboxylate

Product 1

HCID 71086918(S)-2-{4-[(4-Cyano-pyridine-2-carbonyl)-amino]-3-fluoro-phenyl}-morpholine-4-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(−)-(S)-2-(4-Amino-3-fluoro-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (example 1 h, 70 mg, 236 μmol, Eq: 1.00), 4-cyanopicolinic acid (CAS 640296-19-1, 45.5 mg, 307 μmol, Eq: 1.3) and HBTU (134 mg, 354 μmol, Eq: 1.5) were dissolved in DMF (1.25 ml), treated with N-Methylmorpholin (71.7 mg, 77.9 μl, 709 μmol, Eq: 3) and stirred at r.t. for 17 h. The mixture was diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered off and concentrated under vacuo. The solid residue was diluted with a small volume of MeOH, and filtered, leading to 64 mg of a white solid.

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered off
  5. concentrationconcentrated under vacuo
  6. additionThe solid residue was diluted with a small volume of MeOH
  7. filtrationfiltered

Sources & evidence

ORD record
ord-3ffb5d80f43a48c19b449ad7a0c1c2b0
Source dataset
uspto-grants-2015_05
Patent number
US09029370B2

Reaction notes

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