Ammonia → HCID 178427883, compound

HRID 1749543Notes

Reaction equation

HRID 1749543 reaction equation
[CH3:1][C:2]1([CH3:30])[C@@H:5]([C:6]2[N:10]=[CH:9][N:8](C3CCCCO3)[N:7]=2)[CH2:4][C@H:3]1[NH:17][C:18]1[C:23]([C:24]#[N:25])=[CH:22][N:21]=[C:20](S(C)(=O)=O)[N:19]=1.Cl.[NH2:32][CH2:33][CH2:34][CH:35]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[NH:37][C:36]1=[O:44].CCN(C(C)C)C(C)C.N>CN1C(=O)CCC1.O.Cl.CO>[CH3:30][C:2]1([CH3:1])[C@@H:5]([C:6]2[N:10]=[CH:9][NH:8][N:7]=2)[CH2:4][C@H:3]1[NH:17][C:18]1[C:23]([C:24]#[N:25])=[CH:22][N:21]=[C:20]([NH:32][CH2:33][CH2:34][CH:35]2[C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[NH:37][C:36]2=[O:44])[N:19]=1

Participants

9

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 117012923-(2-aminoethyl)-2,3-dihydro-1H-indol-2-one hydrochlorideHCID 1181621414-(((1R,3S)-2,2-dimethyl-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)cyclobutyl)amino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile

Product 1

HCID 178427883HCID 178427883, compoundYield 23.1%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(((1R,3S)-2,2-dimethyl-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)cyclobutyl)amino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile (140 mg, crude), 3-(2-aminoethyl)indolin-2-one hydrochloride (80 mg, 0.376 mmol) and DIEA (194 mg, 1.50 mmol) in NMP (2.0 mL) was stirred at 100° C. for 1 h. Th reaction was diluted with water and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated to give a crude product, which was dissolved in a solution of hydrochloride in MeOH (2N, 5 mL) and stirred at room temperature for 5 h. The reaction was neutralized with ammonia and concentrated. The residue was purified by standard methods to afford the title compound (33.4 mg, 0.075 mmol, 20% yield for two steps). 1H NMR (400 MHz, DMSO-d6) δ (ppm) 13.49 (brs, 1H), 10.24 (s, 1H), 8.52-7.41 (m, 3H), 7.29 (t, J=7.6 Hz, 1H), 7.25-7.07 (m, 2H), 7.01-6.93 (m, 1H), 6.87-6.82 (m, 1H), 4.41-4.29 (m, 1H), 3.59-3.43 (m, 2H), 3.42-3.25 (m, 1H), 3.10-2.96 (m, 1H), 2.81-2.66 (m, 1H), 2.49-2.34 (m, 1H), 2.16-1.94 (m, 2H), 1.49-1.00 (m, 3H), 0.63-0.62 (m, 3H). MS (ESI) m/z 444.2 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customto give a crude product, which
  5. stirringstirred at room temperature for 5 h
  6. concentrationconcentrated
  7. customThe residue was purified by standard methods

Sources & evidence

ORD record
ord-db41da5666fa4344b1608451da6fa57a
Source dataset
uspto-grants-2015_10
Patent number
US09156798B2

Reaction notes

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