Lithium hydroxide, monohydrate → HCID 58431331, compound

HRID 1617417Notes

Reaction equation

HRID 1617417 reaction equation
C([O:4][CH2:5][C:6]1[CH:11]=[C:10]([C:12]([N:14]2[CH2:19][CH2:18][CH:17]([N:20]3[CH2:23][C:22]([CH2:46][C:47]#[N:48])([N:24]4[CH:28]=[C:27]([C:29]5[C:30]6[CH:37]=[CH:36][N:35]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[C:31]=6[N:32]=[CH:33][N:34]=5)[CH:26]=[N:25]4)[CH2:21]3)[CH2:16][CH2:15]2)=[O:13])[N:9]=[C:8]([C:49]([F:52])([F:51])[F:50])[N:7]=1)(=O)C.O.[OH-].[Li+]>C1COCC1.O>[OH:4][CH2:5][C:6]1[N:7]=[C:8]([C:49]([F:51])([F:50])[F:52])[N:9]=[C:10]([C:12]([N:14]2[CH2:19][CH2:18][CH:17]([N:20]3[CH2:23][C:22]([CH2:46][C:47]#[N:48])([N:24]4[CH:28]=[C:27]([C:29]5[C:30]6[CH:37]=[CH:36][N:35]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:43])([CH3:44])[CH3:45])[C:31]=6[N:32]=[CH:33][N:34]=5)[CH:26]=[N:25]4)[CH2:21]3)[CH2:16][CH2:15]2)=[O:13])[CH:11]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 58431357HCID 58431357, compound

Product 1

HCID 58431331HCID 58431331, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [6-[(4-{3-(cyanomethyl)-3-[4-(7-{[2-trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl)carbonyl]-2-(trifluoromethyl)pyrimidin-4-yl]methyl acetate (0.85 g, 1.15 mmol, from Step D) in THF (16 mL) at room temperature was added a solution of lithium hydroxide, monohydrate (0.072 g, 1.7 mmol) in water (4 mL). The reaction was stirred for 45 minutes, then was neutralized by the addition of 1N HCl and the product was extracted with ethyl acetate. The extracts were combined and dried over sodium sulfate, decanted and concentrated to afford a yellow foam, which was used without further purification. Yield: 0.72 g (90%); LC-MS: 697.2 (M+H)+. 1H NMR (300 MHz, CDCl3): δ 8.86 (s, 1H), 8.44 (s, 1H), 8.31 (s, 1H), 7.92 (s, 1H), 7.42 (d, 1H), 6.81 (d, 1H), 5.68 (s, 2H), 4.92 (s, 2H), 4.28-4.17 (m, 1H), 3.89-3.71 (m, 3H), 3.71-3.61 (m, 2H), 3.55 (dd, 2H), 3.47-3.34 (m, 3H), 3.33-3.21 (m, 1H), 2.68-2.53 (m, 1H), 1.93-1.68 (m, 2H), 1.60-1.41 (m, 2H), 0.92 (dd, 2H), −0.06 (s, 9H).

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. dry with materialdried over sodium sulfate
  3. customdecanted
  4. concentrationconcentrated
  5. customto afford a yellow foam, which
  6. customwas used without further purification

Sources & evidence

ORD record
ord-d49c2f116a454ca69e9b31c222a48561
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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