Lithium hydroxide, monohydrate → HCID 53380869, compound

HRID 1617419Notes

Reaction equation

HRID 1617419 reaction equation
O.[OH-].[Li+].C([O:7][CH2:8][C:9]1[CH:14]=[C:13]([C:15]([N:17]2[CH2:22][CH2:21][CH:20]([N:23]3[CH2:26][C:25]([CH2:49][C:50]#[N:51])([N:27]4[CH:31]=[C:30]([C:32]5[C:33]6[CH:40]=[CH:39][N:38](COCC[Si](C)(C)C)[C:34]=6[N:35]=[CH:36][N:37]=5)[CH:29]=[N:28]4)[CH2:24]3)[CH2:19][CH2:18]2)=[O:16])[N:12]=[C:11]([C:52]([F:55])([F:54])[F:53])[N:10]=1)(=O)C>O.O1CCCC1>[OH:7][CH2:8][C:9]1[N:10]=[C:11]([C:52]([F:55])([F:54])[F:53])[N:12]=[C:13]([C:15]([N:17]2[CH2:22][CH2:21][CH:20]([N:23]3[CH2:26][C:25]([CH2:49][C:50]#[N:51])([N:27]4[CH:31]=[C:30]([C:32]5[C:33]6[CH:40]=[CH:39][NH:38][C:34]=6[N:35]=[CH:36][N:37]=5)[CH:29]=[N:28]4)[CH2:24]3)[CH2:19][CH2:18]2)=[O:16])[CH:14]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 58431357HCID 58431357, compound

Product 1

HCID 53380869HCID 53380869, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Lithium hydroxide monohydrate (3.6 mg, 0.085 mmol) in water (0.10 mL) was added 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}piperidin-1-yl)carbonyl]-2-(trifluoromethyl)pyrimidin-4-yl]methyl acetate (21 mg, 0.028 mmol, from Example 376, Step D) in tetrahydrofuran (0.40 mL). The mixture was stirred for 5 minutes and was then treated with 1N HCl to neutralize. Solvent was then removed in vacuo. The residue was stirred in a solution of 1:1 TFA/DCM for one hour, then solvents were removed in vacuo again. The residue was redissolved in MeOH (1 mL) and ethylenediamine (0.2 mL) was added. When deprotection was complete, the product was purified via preparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH). Yield: 0.004 g (25%); LC-MS: 567.3 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ 12.14 (br s, 1H), 8.82 (s, 1H), 8.69 (s, 1H), 8.42 (s, 1H), 7.90 (s, 1H), 7.61 (d, 1H), 7.06 (d, 1H), 5.94 (br s, 1H), 4.71 (s, 2H), 4.12-4.02 (m, 1H), 3.75 (dd, 2H), 3.63-3.46 (m, 5H), 3.31-3.22 (m, 1H), 3.17-3.07 (m, 1h), 2.61-2.53 (m, 1H), 1.84-1.75 (m, 1H), 1.71-1.61 (m, 1H), 1.37-1.18 (m, 2H). 19F NMR (400 MHz, DMSO-d6): δ −69.46 (s, 3F).

Workup

  1. customSolvent was then removed in vacuo
  2. stirringThe residue was stirred in a solution of 1:1 TFA/DCM for one hour
  3. customsolvents were removed in vacuo again
  4. dissolutionThe residue was redissolved in MeOH (1 mL)
  5. additionethylenediamine (0.2 mL) was added
  6. customthe product was purified via preparative HPLC-MS (C18
  7. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-55bf7fc8bd084ca092a72de2e3b2ba24
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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