Lithium hydroxide, monohydrate → HCID 68282987, compound

HRID 1473099Notes

Reaction equation

HRID 1473099 reaction equation
C[O:2][C:3](=[O:41])[CH2:4][C:5]1[CH:40]=[CH:39][CH:38]=[CH:37][C:6]=1[CH2:7][CH2:8][C:9]1[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][N:12]=[C:11]([NH:19][C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[CH2:26][N:25]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:24][CH2:23]3)[N:10]=1.O.[OH-].[Li+:44]>C1COCC1.O>[C:33]([O:32][C:30]([N:25]1[CH2:24][CH2:23][C:22]2[C:27](=[CH:28][CH:29]=[C:20]([NH:19][C:11]3[N:10]=[C:9]([CH2:8][CH2:7][C:6]4[CH:37]=[CH:38][CH:39]=[CH:40][C:5]=4[CH2:4][C:3]([O-:41])=[O:2])[C:14]([C:15]([F:17])([F:16])[F:18])=[CH:13][N:12]=3)[CH:21]=2)[CH2:26]1)=[O:31])([CH3:36])([CH3:34])[CH3:35].[Li+:44]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 71217519HCID 71217519, compound

Product 1

HCID 68282987HCID 68282987, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 6-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3,4-dihydroisoquinoline-2(1H)-carboxylate (I80) (520 mg, 0.91 mmol) was dissolved in THF (20 mL) and a solution of lithium hydroxide hydrate (76 mg. 1.8 mmol) in water (5 mL) was added. After 18 hours the THF was removed under reduced pressure, the mixture was diluted with water (10 mL) and extracted with ethyl acetate (3×50 mL). The combined ethyl acetate phases were washed with brine, dried (sodium sulfate) and evaporated to give the title compound (I81) (414 mg, 81% yield) as a yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.36 (s, 1H), 8.65 (s, 1H), 7.64 (s, 1H), 7.59 (d, J=8.4 Hz, 1H), 7.20-7.02 (m, 5H), 4.45 (5, 2H), 3.54 (t, J=5.8 Hz, 2H), 3.17 (s, 2H), 3.14-2.98 (m, 4H), 2.76 (t, J=5.7 Hz, 2H), 1.43 (s, 9H). LCMS Method C: rt 6.51 min; m/z 557.1 [M−Li+2H] 501.1 [M−tBu−Li+3H]+, 457.1 [M−Li−Boc+3H]+; m/z 555.1 [M−Li]−.

Workup

  1. customAfter 18 hours the THF was removed under reduced pressure
  2. additionthe mixture was diluted with water (10 mL)
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washThe combined ethyl acetate phases were washed with brine
  5. dry with materialdried (sodium sulfate)
  6. customevaporated

Sources & evidence

ORD record
ord-20bc530c798b4f028c7e1a36d3c83cd1
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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