Difluoroacetic acid → (R)-1-(2-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholino)-2,2-difluoroethanone

HRID 57594

Reaction equation

HRID 57594 reaction equation
[Cl:1][C:2]1[N:11]=[C:10]([NH:12][CH2:13][C@H:14]2[O:19][CH2:18][CH2:17][N:16]([C:20]([O:22]C(C)(C)C)=O)[CH2:15]2)[C:9]2[C:4](=[N:5][CH:6]=[CH:7][N:8]=2)[CH:3]=1.[F:27][CH:28]([F:32])C(O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>Cl.C(OCC)(=O)C>[Cl:1][C:2]1[N:11]=[C:10]([NH:12][CH2:13][C@@H:14]2[CH2:15][N:16]([C:20](=[O:22])[CH:28]([F:32])[F:27])[CH2:17][CH2:18][O:19]2)[C:9]2[C:4](=[N:5][CH:6]=[CH:7][N:8]=2)[CH:3]=1

Participants

7

Reactant 4

HCID 9788Difluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86706988(R)-tert-butyl 2-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholine-4-carboxylate

Product 1

HCID 86717395(R)-1-(2-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholino)-2,2-difluoroethanoneYield 73.4%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

The (R)-tert-butyl 2-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholine-4-carboxylate (3.00 g, 8.0 mmol) was dissolved in the solution of HCl in ethyl acetate (20 mL), and the mixture was stirred at room temperature for 2 hours until TLC indicated Boc group was removed. The volatile materials were removed in vacuo and the residues were dissolved in dichloromethane. To the solution, difluoroacetic acid (1.15 g, 12 mmol), HATU (7.60 g, 20.0 mmol) and DIPEA (6.20 g, 48.0 mmol) were added subsequently and stirred at room temperature overnight. The mixture was purified by C18 column chromatography to give the desired amide as yellow solid (2.1 g). MS (m/z): 358 (M+H)+

Workup

  1. customwas removed
  2. customThe volatile materials were removed in vacuo
  3. dissolutionthe residues were dissolved in dichloromethane
  4. stirringstirred at room temperature overnight
  5. customThe mixture was purified by C18 column chromatography

Sources & evidence

ORD record
ord-af6f85c86d074fb0b57f5217055f1022
Source dataset
uspto-grants-2016_09
Patent number
US09434726B2

Linked notes

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