Water → HCID 72706843, compound

HRID 1750279Notes

Reaction equation

HRID 1750279 reaction equation
CC1C=CC(S([N:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([N:20]4[CH2:25][CH2:24][CH2:23][C@H:22]([CH3:26])[CH2:21]4)[C:14]=3[C:13]([C:27]3[CH:28]=[C:29]([CH2:33][OH:34])[CH:30]=[CH:31][CH:32]=3)=[CH:12]2)(=O)=O)=CC=1.O.[OH-].[Li+].O>CC(O)C>[CH3:26][C@H:22]1[CH2:23][CH2:24][CH2:25][N:20]([C:19]2[C:14]3[C:13]([C:27]4[CH:28]=[C:29]([CH2:33][OH:34])[CH:30]=[CH:31][CH:32]=4)=[CH:12][NH:11][C:15]=3[N:16]=[CH:17][N:18]=2)[CH2:21]1

Participants

5

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 86706954HCID 86706954, compound

Product 1

HCID 72706843HCID 72706843, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a stirred solution of (3-{7-[(4-methylphenyl)sulfonyl]-4-[(3S)-3-methylpiperidin-1-yl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}phenyl)methanol (C16) from the previous step (<0.50 mmol) in 2-propanol (20 mL) was added lithium hydroxide monohydrate (0.42 g, 10 mmol) and water (3 mL) and the reaction mixture was stirred at room temperature for 18 hours. After concentration in vacuo, the residue was purified by preparative HPLC (Column: Waters XBridge; Mobile phase A: 0.1% ammonia in water; Mobile phase B: acetonitrile; Gradient: 44% to 60% B) to provide the product as a white solid. Yield: 130 mg, 0.403 mmol, 80% over two steps. LCMS m/z 323.4 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 8.24 (s, 1H), 7.46 (br s, 1H), 7.35-7.43 (m, 2H), 7.30 (br d, J=6 Hz, 1H), 7.23 (s, 1H), 4.67 (s, 2H), 3.89 (br d, J=13 Hz, 1H), 3.79 (br d, J=12 Hz, 1H), 2.58-2.69 (m, 1H), 2.27 (dd, J=12.0, 11.0 Hz, 1H), 1.62-1.71 (m, 1H), 1.30-1.52 (m, 3H), 0.87-1.01 (m, 1H), 0.60 (d, J=6.5 Hz, 3H).

Workup

  1. concentrationAfter concentration in vacuo
  2. customthe residue was purified by preparative HPLC (Column: Waters XBridge; Mobile phase A: 0.1% ammonia in water; Mobile phase B: acetonitrile; Gradient: 44% to 60% B)

Sources & evidence

ORD record
ord-77b6ac8bef0c48d2a1b57c9d2b3ec3d8
Source dataset
uspto-grants-2015_10
Patent number
US09156845B2

Reaction notes

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