4-Methylmorpholine → HCID 59610139, compound

HRID 2382255Notes

Reaction equation

HRID 2382255 reaction equation
[O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][C:8]([OH:10])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:35][C:36]1[CH:65]=[CH:64][C:39]([C:40]([NH:42][C:43]2[CH:44]=[C:45]([C:57]3[CH:62]=[CH:61][C:60]([F:63])=[CH:59][CH:58]=3)[CH:46]=[CH:47][C:48]=2[NH:49]C(=O)OC(C)(C)C)=[O:41])=[CH:38][CH:37]=1.CN1CCOCC1>CN(C=O)C.O.C(#N)C>[NH2:49][C:48]1[CH:47]=[CH:46][C:45]([C:57]2[CH:58]=[CH:59][C:60]([F:63])=[CH:61][CH:62]=2)=[CH:44][C:43]=1[NH:42][C:40](=[O:41])[C:39]1[CH:64]=[CH:65][C:36]([NH:35][C:8](=[O:10])[CH2:7][N:3]2[CH2:4][CH2:5][CH2:6][C:2]2=[O:1])=[CH:37][CH:38]=1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 31466872-(2-Oxopyrrolidin-1-yl)acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67128321HCID 67128321, compound

Product 1

HCID 59610139HCID 59610139, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

To the 2-(2-oxopyrrolidin-1-yl)acetic acid (186 mgs, 1.3 mmol) in DMF (3 mL), was added HATU (570 mg, 1.5 mmol), tert-butyl 3-(4-aminobenzamido)-4′-fluorobiphenyl-4-ylcarbamate (421 mg, 1.0 mmol) and NMM (0.3 mL, 3.0 mmol) and stirred at 55° C. for 40 hours. The reaction mixture was then diluted with water and acetonitrile and the precipitate was filtered, washed with water and dried and used further without purification. To the above BOC protected compound, 4.0 M HCl dioxane (7 mL) was added and stirred at room temperature for 2 hour. The reaction mixture was then diluted with ether and stirred. The resulting solid was filtered, washed with ether and dried to give the title compound. C25H23FN4O3 446.9 (M+1). 1H NMR (400 MHz, DMSO-d6): δ 10.60 (s, 2H); 8.12 (d, J=8.4 Hz, 2H); 7.86 (s, 1H); 7.75 (d, J=8.4 Hz, 2H); 7.73-7.68 (m, 2H); 7.61-7.56 (m, 2H); 7.31 (m, 2H); 4.07 (s, 2H); 3.43-3.40 (m, 2H); 3.44-3.39 (m, 1H); 2.24-2.22 (m, 2H); 1.98-1.92 (m, 2H).

Workup

  1. filtrationthe precipitate was filtered
  2. washwashed with water
  3. customdried
  4. customused further without purification
  5. additionTo the above BOC protected compound, 4.0 M HCl dioxane (7 mL) was added
  6. stirringstirred at room temperature for 2 hour
  7. additionThe reaction mixture was then diluted with ether
  8. stirringstirred
  9. filtrationThe resulting solid was filtered
  10. washwashed with ether
  11. customdried

Sources & evidence

ORD record
ord-d4371a972e4b4498a447a5edcd746930
Source dataset
uspto-grants-2012_09
Patent number
US08258316B2

Reaction notes

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