Morpholine → HCID 44553423, compound

HRID 2359402Notes

Reaction equation

HRID 2359402 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[C:12]([NH:19][C:20]([C:22]4[N:23]=[CH:24][S:25][CH:26]=4)=[O:21])[CH:13]=[CH:14][CH:15]=3)[N:10]=2)[CH:6]=[CH:7][CH:8]=1)=O.[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[BH4-].[Na+]>C1COCC1.C(O)C.C(O)(=O)C>[O:30]1[CH2:31][CH2:32][N:27]([CH2:1][C:3]2[CH:4]=[C:5]([C:9]3[CH:18]=[CH:17][C:16]4[C:11](=[C:12]([NH:19][C:20]([C:22]5[N:23]=[CH:24][S:25][CH:26]=5)=[O:21])[CH:13]=[CH:14][CH:15]=4)[N:10]=3)[CH:6]=[CH:7][CH:8]=2)[CH2:28][CH2:29]1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 4311764Sodium borohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 58154761HCID 58154761, compound

Product 1

HCID 44553423HCID 44553423, compoundYield 71.2%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-(2-(3-formylphenyl)quinolin-8-yl)thiazole-4-carboxamide (54 mg, 0.150 mmol) and morpholine (37 μL, 0.450 mmol) in a mixture of THF (4 mL) and Ethanol (8 mL) was added Na(OAc)3BH (95 mg, 0.450 mmol). The reaction was stirred 18 hours, and NaBH4 (17 mg, 3 eq) and acetic acid (500 uL) and the reaction was stirred for 2 hours. The reaction was quenched with water/methanol mixture, concentrated to dryness, and diluted with CH2Cl2. The resulting solution was washed with 1N NaOH, water, brine, dried (Na2SO4) and concentrated. The crude material was purified by silica gel column chromatography (0 to 10% methanol gradient in CH2Cl2 modified with 0.1% triethylamine). The product was lyophilized in a mixture of acetonitrile/water to obtain N-(2-(3-(morpholinomethyl)phenyl)quinolin-8-yl)thiazole-4-carboxamide (46 mg, 71% yield). MS (ESI) calcd for C24H22N4O2S (m/z): 430.15. found: 431 [M+1].

Workup

  1. customThe reaction was quenched with water/methanol mixture
  2. concentrationconcentrated to dryness
  3. additiondiluted with CH2Cl2
  4. washThe resulting solution was washed with 1N NaOH, water, brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel column chromatography (0 to 10% methanol gradient in CH2Cl2 modified with 0.1% triethylamine)
  8. additionThe product was lyophilized in a mixture of acetonitrile/water

Sources & evidence

ORD record
ord-da51089084c245f5be39a3ecd49881c0
Source dataset
uspto-grants-2014_04
Patent number
US08685970B2

Reaction notes

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