Hydrochloric Acid → tert-butyl (6S,7S)-6-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2.5]octane-7-carboxylate

HRID 1477385Notes

Reaction equation

HRID 1477385 reaction equation
[CH3:1][C:2]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.Cl.[C:22]([O:26][C:27]([C@H:29]1[CH2:36][C:33]2([CH2:35][CH2:34]2)[CH2:32][NH:31][C@@H:30]1[C:37](O)=[O:38])=[O:28])([CH3:25])([CH3:24])[CH3:23].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[CH3:1][C:2]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:15]=[CH:16][C:17]([NH:20][C:37]([C@@H:30]3[C@@H:29]([C:27]([O:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:28])[CH2:36][C:33]4([CH2:34][CH2:35]4)[CH2:32][NH:31]3)=[O:38])=[CH:18][CH:19]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 16108946HCID 16108946, compoundHCID 223927834-((2-Methylquinolin-4-yl)methoxy)aniline

Product 1

HCID 67006804tert-butyl (6S,7S)-6-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2.5]octane-7-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

4-(2-Methylquinolin-4-ylmethoxy)phenylamine as an HCl salt (94.0 mg, 0.28 mmol) and (6S,7S)-7-(tert-butoxycarbonyl)-5-azaspiro[2.5]octane-6-carboxylic acid (70.0 mg, 0.27 mmol) were dissolved in DMF (2.0 mL). BOP (143.0 mg, 0.32 mmol) was added to the above solution and then cooled to 0° C. Diisopropylethylamine (0.175 mL, 1.0 mmol) was added to the above mixture at 0° C. and then the reaction was stirred at room temperature for 2 h. The mixture was diluted with water, extracted with ethyl acetate, the combined extract was washed with brine, dried and concentrated. The crude tert-butyl(6S,7S)-6-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2.5]octane-7-carboxylate (140 mg) was used in the next step without purification. ESI (M+H)+502.4.

Workup

  1. extractionextracted with ethyl acetate
  2. extractionthe combined extract
  3. washwas washed with brine
  4. customdried
  5. concentrationconcentrated
  6. customThe crude tert-butyl(6S,7S)-6-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2.5]octane-7-carboxylate (140 mg) was used in the next step without purification

Sources & evidence

ORD record
ord-fc32b508f67c4eaabf0e676d485f42ee
Source dataset
uspto-grants-2016_08
Patent number
US09403775B2

Reaction notes

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