Diisobutylaluminum hydride → HCID 57955156, compound

HRID 73690Notes

Reaction equation

HRID 73690 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]4[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=4[F:36])=[O:24])=[CH:18][CH:17]=3)[C:9]([CH2:13][O:14][CH3:15])=[C:10]([CH:11]=[O:12])[N:6]2[N:5]=[CH:4][N:3]=1.CC(C[AlH]CC(C)C)C>C1COCC1.C(OCC)(=O)C>[NH2:1][C:2]1[C:7]2=[C:8]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]4[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[CH:28][C:27]=4[F:36])=[O:24])=[CH:18][CH:17]=3)[C:9]([CH2:13][O:14][CH3:15])=[C:10]([CH2:11][OH:12])[N:6]2[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 57955296N-{4-[4-amino-7-formyl-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N'-[2-fluoro-5-(trifluoro-methyl)phenyl]urea

Product 1

HCID 57955156HCID 57955156, compoundYield 49.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of Intermediate AW (N-{4-[4-amino-7-formyl-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoro-methyl)phenyl]urea (50 mg, 0.1 mmol)) in THF at −78° C. under N2 was added DIBAL-H (0.5 ml, 0.5 mmol). The reaction mixture was stirred for 30 min. and was allowed to warm up to 0° C. The reaction was diluted with ethyl acetate (5 mL) and quenched with aqueous saturated Rochelle's salt (5 ml). The reaction mixture was stirred for 10 min at 0° C. and then warmed to rt. The organic layer was collected and washed with aqueous Rochelle's salt (2×), dried (Na2SO4) and concentrated. The crude concentrate was purified via column chromatography (5:95, v/v MeOH—CH2Cl2) to afford 25 mg of the title compound (yield 49%). 1H-NMR (DMSO-d6) δ9.32 (s, 1H), 8.96 (d, J=3 Hz, 1H), 8.63 (d, J=5 Hz, 1H), 7.90 (s, 1H), 7.58 (d, J=7 Hz, 2H), 7.50 to 7.32 (m, 3H), 5.0 (t, J=5 Hz, 1H), 4.79 (d, J=5 Hz, 2H), 4.30 (s, 3H), 3.16 (s, 2H) ppm; MS [M+H]+=505.1; LCMS RT=2.66 min.

Workup

  1. customquenched with aqueous saturated Rochelle's salt (5 ml)
  2. stirringThe reaction mixture was stirred for 10 min at 0° C.
  3. temperaturewarmed to rt
  4. customThe organic layer was collected
  5. washwashed with aqueous Rochelle's salt (2×)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. concentrationThe crude concentrate
  9. customwas purified via column chromatography (5:95, v/v MeOH—CH2Cl2)

Sources & evidence

ORD record
ord-9a8318a75107467a94343658a2f1fb7f
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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