Morpholine → HCID 178461955, compound

HRID 243463Notes

Reaction equation

HRID 243463 reaction equation
[CH:1]1([N:4]2[C:8]3[C:9]([C:14]([OH:16])=O)=[C:10]([F:13])[CH:11]=[CH:12][C:7]=3[N:6]=[C:5]2[C@@H:17]([NH:19][C:20]2[N:28]=[CH:27][N:26]=[C:25]3[C:21]=2[N:22]=[CH:23][N:24]3C2CCCCO2)[CH3:18])[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:59]1[CH2:64][CH2:63][O:62][CH2:61][CH2:60]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH:1]1([N:4]2[C:8]3[C:9]([C:14]([N:59]4[CH2:64][CH2:63][O:62][CH2:61][CH2:60]4)=[O:16])=[C:10]([F:13])[CH:11]=[CH:12][C:7]=3[N:6]=[C:5]2[C@@H:17]([NH:19][C:20]2[N:28]=[CH:27][N:26]=[C:25]3[C:21]=2[N:22]=[CH:23][NH:24]3)[CH3:18])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68157183HCID 68157183, compound

Product 1

HCID 178461955HCID 178461955, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-cyclopropyl-5-fluoro-2-{(S)-1-[9-(tetrahydropyran-2-yl)-9H-purin-6-ylamino]ethyl}-3H-benzoimidazole-4-carboxylic acid (64 mg, 0.14 mmol), HATU (63 mg, 0.17 mmol), morpholine (18 μL, 0.216 mmol) and DIPEA (47 μL, 0.28 mmol) in DCM (2 mL) was stirred at RT for 1 h. The crude mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM) to afford 389 (46 mg, 75%) as a white solid. LCMS (Method K): RT 2.49 and 2.53 min [M+H]+ 451.05. 1H NMR (DMSO-d6, 400 MHz): δ 8.24-7.83 (3H, m), 7.69-7.60 (1H, m), 7.10 (1H, t, J=9.53 Hz), 6.07-5.84 (1H, m), 3.90-3.83 (1H, m), 3.80-3.72 (1H, m), 3.69-3.59 (2H, m), 3.59-3.50 (2H, m), 3.41-3.35 (2H, m), 3.28-3.20 (1H, m), 1.72-1.63 (3H, m), 1.26-0.85 (4H, m)

Workup

  1. washwas washed with MeOH
  2. concentrationconcentrated in vacuo
  3. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-3d161c90ec944c4f9c709945e91b5f02
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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