Morpholine → HCID 16117890, compound

HRID 1162259Notes

Reaction equation

HRID 1162259 reaction equation
[S:1]1[CH:5]=[C:4]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([NH:16][C:17]4[C:26]5[C:21](=[CH:22][CH:23]=[CH:24][C:25]=5[O:27][C@H:28]([CH3:32])[C:29]([OH:31])=O)[N:20]=[CH:19][N:18]=4)=[CH:13][CH:14]=3)[CH:9]=[N:8]2)[N:3]=[CH:2]1.OC1C=CC=C[N+]=1[O-].[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1.C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[CH3:32][C@@H:28]([O:27][C:25]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:26]=1[C:17]([NH:16][C:12]1[CH:11]=[C:10]3[C:15](=[CH:14][CH:13]=1)[N:7]([CH2:6][C:4]1[N:3]=[CH:2][S:1][CH:5]=1)[N:8]=[CH:9]3)=[N:18][CH:19]=[N:20]2)[C:29]([N:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1)=[O:31]

Participants

7

Reactant 5

HCID 8083MorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 68620045HCID 68620045, compoundHCID 178526252HCID 178526252, compound

Product 1

HCID 16117890HCID 16117890, compoundYield 62.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (2R)-2-[(4-{[1-(1,3-thiazol-4-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoic acid (250 mg, 0.56 mmol), 2-hydroxypyridine-N-oxide (124 mg, 1.1 mmol), morpholine (0.098 ml, 1.1 mmol), diisopropylethylamine (0.195 ml, 1.1 mmol) and EDCI (214 mg, 1.1 mmol) in DMF (2 ml) was stirred at room temperature for 18 hours. Additional coupling agents were added (1 equivalent) and the mixture was stirred for 2 hours more. The reaction mixture was directly injected on an HPLC column (C18, 5 microns, 20 mm diameter, 100 mm length) of a preparative HPLC-MS system eluting with a mixture of water and acetonitrile containing 2 g/l of ammonium carbonate (gradient) to give the title compound as a white solid (180 mg, 62%); NMR Spectrum 1.58 (d, 3H), 3.70-3.40 (m, 8H), 5.79 (s, 2H), 5.88 (q, 1H), 7.29 (d, 1H), 7.35 (s, 1H), 7.51 (s, 1H), 7.75 (m, 2H), 7.84 (m, 1H), 8.10 (s, 1H), 8.51 (s, 2H), 9.04 (s, 1H), 11.12 (br s, 1H); Mass spectrum: MH+ 516.

Workup

  1. additionwere added (1 equivalent)
  2. stirringthe mixture was stirred for 2 hours more
  3. washeluting with a mixture of water and acetonitrile containing 2 g/l of ammonium carbonate (gradient)

Sources & evidence

ORD record
ord-b5e12b37c5d84c1f96194839cf7d1398
Source dataset
uspto-grants-2010_10
Patent number
US07820683B2

Reaction notes

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