1,4-Dioxa-8-azaspiro(4.5)decane → 5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [2-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-1-(S)-(4-fluorobenzyl)-2-oxoethyl]amide

HRID 751721Notes

Reaction equation

HRID 751721 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]([NH:13][C@@H:14]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:15]([OH:17])=O)=[O:12])[NH:8][C:5]2=[CH:6][N:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:50]1[O:59][C:53]2([CH2:58][CH2:57][NH:56][CH2:55][CH2:54]2)[O:52][CH2:51]1.CCN(C(C)C)C(C)C>CN(C=O)C>[O:52]1[C:53]2([CH2:58][CH2:57][N:56]([C:15](=[O:17])[C@@H:14]([NH:13][C:11]([C:9]3[NH:8][C:5]4=[CH:6][N:7]=[C:2]([Cl:1])[CH:3]=[C:4]4[CH:10]=3)=[O:12])[CH2:18][C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)[CH2:55][CH2:54]2)[O:59][CH2:50][CH2:51]1

Participants

6

Reactant 4

HCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 597536992-(S)-[(5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)propionic acid

Product 1

HCID 113063145-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [2-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-1-(S)-(4-fluorobenzyl)-2-oxoethyl]amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(S)-[(5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)propionic acid (EXAMPLE 228, 40 mg, 0.11 mmol) in DMF (4 mL) was added HATU (50 mg, 0.13 mmol) and the reaction stirred for 10 min. 4-Piperidone ethylene ketal (19 mg, 0.13 mmol) was added, followed by DIPEA (23 μL, 0.13 mmol) and the reaction stirred at rt for 16 h. Solvent was removed in vacuo and the crude material partitioned between ethyl acetate (15 mL) and water (15 mL). The organic layer was washed with 1M HCl solution (15 mL), sodium bicarbonate solution (2×20 mL) then brine (2×20 mL), dried (MgSO4) and the solvent removed in vacuo. Purification by chromatography using dichloromethane/methanol (9:1) as the eluent gave the title compound as a pale yellow powder. (ES+)=487.30 [M+H]+; RT=3.28 min.

Workup

  1. stirringthe reaction stirred at rt for 16 h
  2. customSolvent was removed in vacuo
  3. customthe crude material partitioned between ethyl acetate (15 mL) and water (15 mL)
  4. washThe organic layer was washed with 1M HCl solution (15 mL), sodium bicarbonate solution (2×20 mL)
  5. dry with materialbrine (2×20 mL), dried (MgSO4)
  6. customthe solvent removed in vacuo
  7. customPurification by chromatography

Sources & evidence

ORD record
ord-9a56c8c6b0754df0abbf6154b46a8353
Source dataset
uspto-grants-2008_07
Patent number
US07405210B2

Reaction notes

Loading…