Aluminium lithium hydride → HCID 58169370, compound

HRID 1484936Notes

Reaction equation

HRID 1484936 reaction equation
[C:1]([NH:5][S:6]([C:9]1[S:10][C:11]([C:14]2[N:19]=[C:18]([NH:20][C:21]3[CH:25]=[C:24]([CH:26]4[CH2:28][CH2:27]4)[NH:23][N:22]=3)[C:17]([C:29]#[C:30][CH2:31][OH:32])=[CH:16][N:15]=2)=[CH:12][CH:13]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[C:1]([NH:5][S:6]([C:9]1[S:10][C:11]([C:14]2[N:19]=[C:18]([NH:20][C:21]3[CH:25]=[C:24]([CH:26]4[CH2:28][CH2:27]4)[NH:23][N:22]=3)[C:17](/[CH:29]=[CH:30]/[CH2:31][OH:32])=[CH:16][N:15]=2)=[CH:12][CH:13]=1)(=[O:7])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 50943776HCID 50943776, compound

Product 1

HCID 58169370HCID 58169370, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of N-tert-butyl-5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(3-hydroxyprop-1-ynyl) pyrimidin-2-yl)thiophene-2-sulfonamide (250 mg, 0.53 mmol, 1.0 eq) in dry THF (2 mL) was added dropwise over 10 min to a mixture of LiAlH4 (250 mg, 6.58 mmol, 12.4 eq) in THF (20 mL) under nitrogen. The reaction mixture was maintained 0° C. during the addition. The reaction mixture was heated to reflux for 10 min. Then the reaction mixture was cooled to 0° C., while vigorous stirring was maintained, carefully treated with Na2SO4.10H2O (10 g) in portion and then stirred at room temperature for 10 min. The reaction mixture was filtered. The filtrate was concentrated and purified by silica gel chromatography (EtOAc/MeOH/THF from 10:0:0 to 20:1:2) to afford (E)-N-tert-butyl-5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(3-hydroxyprop-1-enyl)pyrimidin-2-yl)thiophene-2-sulfonamide (Compound 218) (100 mg, 40.0%). LC-MS (m/z)=475 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.74-0.75 (m, 2H), 0.96-0.97 (m, 2H), 1.20 (s, 9H), 1.90-1.95 (m, 1H), 4.16 (m, 2H), 4.85 (s, 1H), 6.38 (d, J=16.0 Hz, 1H), 6.46 (s, 1H), 6.89 (d, J=15.2 Hz, 1H), 7.59 (d, J=3.6 Hz, 1H), 7.73 (d, J=4.0 Hz, 1H), 7.87 (bs, 1H), 8.42 (s, 1H), 9.26 (bs, 1H), 12.18 (bs, 1H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 10 min
  3. temperatureThen the reaction mixture was cooled to 0° C.
  4. temperaturewas maintained
  5. stirringstirred at room temperature for 10 min
  6. filtrationThe reaction mixture was filtered
  7. concentrationThe filtrate was concentrated
  8. custompurified by silica gel chromatography (EtOAc/MeOH/THF from 10:0:0 to 20:1:2)

Sources & evidence

ORD record
ord-0dd89582cf7e435bb1915f631759687c
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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