Sodium Carbonate → HCID 178428380, compound

HRID 1641307Notes

Reaction equation

HRID 1641307 reaction equation
[CH:1]1([NH:7][C:8]2[C:12]3([CH2:17][CH2:16][N:15]([CH2:18][C:19]4[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=4)[CH2:14][CH2:13]3)[N:11]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=3)[C:10](=[O:35])[N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:37]1[CH:38]=[N:39][CH:40]=[CH:41][C:42]=1[CH3:43].CC1C=C(C)C(P(C2C(C)=CC(C)=C(S([O-])(=O)=O)C=2)C2C(C)=CC(C)=C(S([O-])(=O)=O)C=2)=CC=1S([O-])(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>CC#N.CC(O)=O.CC(O)=O.[Pd].O>[CH:1]1([NH:7][C:8]2[C:12]3([CH2:17][CH2:16][N:15]([CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:37]5[CH:38]=[N:39][CH:40]=[CH:41][C:42]=5[CH3:43])[CH:20]=4)[CH2:14][CH2:13]3)[N:11]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=3)[C:10](=[O:35])[N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 8176303-Bromo-4-methylpyridineHCID 21574707HCID 21574707, compoundHCID 178517966HCID 178517966, compound

Product 1

HCID 178428380HCID 178428380, compound

Reagents, catalysts & solvents 3

HCID 4144353Palladium (II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 0.100 g (0.209 mmol) 3-{[4-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxo-1,3,8-triazaspiro[4.5]dec-3-en-8-yl]methyl}phenylboronic acid (7-1) in 1 mL CH3CN:H2O was added 0.030 g (0.174 mmol) 3-bromo-4-methylpyridine and 0.007 g (0.011 mmol) Tris(4,6-dimethyl-3sulfonatophenyl)phosphine and 0.001 g (0.004 mmol) palladium II acetate and 0.037 g (0.349 mmol) sodium carbonate. The reaction was heated in the microwave at 120° C. for 20 mins. Purification by preparative HPLC (5-95% CH3CN/H2O over 30 min, 0.05% added TFA, C18 PRO YMC 20×150 mm) afforded 4-(cyclohexylamino)-1-(3-fluorophenyl)-8-[3-(4-methylpyridin-3-yl)benzyl]-1,3,8-triazaspiro[4.5]dec-3-en-2-one as a white solid. NMR 1H NMR (CD3OD) δ 8.37 (d, J=5.04 Hz, 1H), 8.29 (s, 1H), 7.42 (m, 3H) 7.19 (m, 6H), 3.76 (m, 1H), 3.47 (s, 2H), 2.77 (m, 2H), 2.29 (s, 3H), 2.14 (m, 6H), 1.95 (m, 2H), 1.77 (m, 2H), 1.66 (m, 1H), 1.36 (m, 4H), 1.18 (m, 1H). High resolution mass spec (FT/ICR) calc M+H=526.2977 found 526.3012.

Workup

  1. customPurification by preparative HPLC (5-95% CH3CN/H2O over 30 min
  2. addition0.05% added TFA

Sources & evidence

ORD record
ord-b9887db8dedd40a08fb3f9addc3af428
Source dataset
uspto-grants-2012_02
Patent number
US08114887B2

Reaction notes

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