Diisopropylamine → 2-[(R)-5-(4-Carbamoyl-phenyl)-indan-1-yl]-2,7-diazaspiro[3.5]nonane-7-carboxylic acid tert-butyl ester

HRID 1913458Notes

Reaction equation

HRID 1913458 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:26][CH2:25][C:11]2([CH2:14][N:13]([C@H:15]3[C:23]4[C:18](=[CH:19][C:20](Br)=[CH:21][CH:22]=4)[CH2:17][CH2:16]3)[CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)(=[O:29])[NH2:28].C1C=C(S([O-])(=O)=O)C=C(P(C2C=CC=C(S([O-])(=O)=O)C=2)C2C=CC=C(S([O-])(=O)=O)C=2)C=1.[Na+].[Na+].[Na+].C(NC(C)C)(C)C>O.C(#N)C.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]([O:5][C:6]([N:8]1[CH2:26][CH2:25][C:11]2([CH2:14][N:13]([C@H:15]3[C:23]4[C:18](=[CH:19][C:20]([C:33]5[CH:34]=[CH:35][C:30]([C:27](=[O:29])[NH2:28])=[CH:31][CH:32]=5)=[CH:21][CH:22]=4)[CH2:17][CH2:16]3)[CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 7912DiisopropylamineHCID 27378114-Aminocarbonylphenylboronic acidHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)HCID 53392276tert-Butyl (R)-2-(5-bromo-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate

Product 1

HCID 674077812-[(R)-5-(4-Carbamoyl-phenyl)-indan-1-yl]-2,7-diazaspiro[3.5]nonane-7-carboxylic acid tert-butyl esterYield 91%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

2-((R)-5-Bromo-indan-1-yl)-2,7-diaza-spiro[3.5]nonane-7-carboxylic acid tert-butyl ester (3-1a, 500 mg, 1.19 mmol), 4-carbamoylphenylboronic acid (587 mg, 3.56 mmol), Pd(OAc)2 (14 mg, 0.06 mmol) and TPPTS ligand (3,3′,3″-phosphinidynetris[benzenesulfonic acid]trisodium salt, 135 mg, 0.24 mmol) were suspended in 10 mL water and 5 mL acetonitrile. Diisopropylamine (291 mg, 2.85 mmol) was added, and the mixture was heated to 90° C. for 2 hours. The mixture was cooled to room temperature and was diluted with ethyl acetate (150 mL). The organic solution was washed with water (50 mL), dried (MgSO4), filtered through Celite® and concentrated to give 499 mg (91%) of the title compound as a light pink powder. MS (ES+) 462.1 (M+H)+. 1H NMR (CD3OD) δ 1.42 (s, 9H), 1.64-1.74 (m, 4H), 1.83-1.96 (m, 1H), 2.17-2.30 (m, 1H), 2.80-2.93 (m, 1H), 3.10 (dt, 1H), 3.24-3.28 (m, 2H), 3.31-3.38 (m, 6H), 4.06 (dd, 1H), 6.79 (d, 1H), 7.39-7.49 (m, 2H), 7.53 (s, 1H), 7.67 (d, 2H), 7.73 (d, 1H), 7.89-7.94 (m, 2H).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. washThe organic solution was washed with water (50 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered through Celite®
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-0bc320bba5e142da954c46986d31841c
Source dataset
uspto-grants-2013_12
Patent number
US08609680B2

Reaction notes

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