Diisobutylaluminum hydride → HCID 86693114, compound

HRID 575086Notes

Reaction equation

HRID 575086 reaction equation
[C:1]([C:4]1[N:5]=[C:6]2[N:16]([CH:17]=1)[CH2:15][CH2:14][O:13][C:12]1[C:7]2=[CH:8][C:9]([C:19]#[C:20][C:21]2([OH:30])[CH2:24][CH:23]([C:25](OCC)=[O:26])[CH2:22]2)=[C:10]([F:18])[CH:11]=1)(=[O:3])[NH2:2].CC(C[AlH]CC(C)C)C>O1CCCC1>[F:18][C:10]1[C:9]([C:19]#[C:20][C:21]2([OH:30])[CH2:22][CH:23]([CH2:25][OH:26])[CH2:24]2)=[CH:8][C:7]2[C:6]3[N:16]([CH2:15][CH2:14][O:13][C:12]=2[CH:11]=1)[CH:17]=[C:4]([C:1]([NH2:2])=[O:3])[N:5]=3

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 86693115HCID 86693115, compound

Product 1

HCID 86693114HCID 86693114, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

Into a 8-mL sealed tube, was placed a solution of ethyl 3-(2-[4-carbamoyl-12-fluoro-9-oxa-3,6-diazatricyclo[8.4.0.0[2,6]]tetradeca-1(14),2,4,10,12-pentaen-13-yl]ethynyl)-3-hydroxycyclobutane-1-carboxylate (140 mg, 0.34 mmol, 1.00 equiv) in tetrahydrofuran (5 mL). Then added DIBAL-H (1.0M in THF, 7 mL, 2.00 equiv) dropwise with stirring at −70° C. The resulting solution was stirred for 4 h at −70° C. The reaction was then quenched by the addition of 2 mL of 10% sodium potassium tartrate. The solids were filtered out. The mixture was diluted with 40 mL of ethyl acetate, and washed with 20 mL of brine, dried over sodium sulfate. Filtered and concentrated, the residue was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-016(Waters)): Column, Xbridge Prep C18, 5 um, 19*150 mm; mobile phase, water with 0.03% NH4CO3 and CH3CN (10% CH3CN up to 29% in 13 min); Detector, uv 254/220 nm. This resulted in 25 mg (20%) of 8-Fluoro-9-(1-hydroxy-3-hydroxymethyl-cyclobutylethynyl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a white solid. (single undetermined diastereomer). LC-MS: (ES, m/z):372[M+H]+ 1H-NMR: (400 MHz, DMSO-d6, ppm) δ 8.602 (d, 1H), 7.785 (s, 1H), 7.596 (s, 1H), 7.142 (s, 1H), 7.033 (d, 1H), 5.907 (s, 1H), 4.559-4.410 (m, 4H), 3.422 (t, 2H), 2.449 (t, 2H), 2.238-2.100 (m, 1H), 2.029 (t, 2H).

Workup

  1. customInto a 8-mL sealed tube
  2. customThe reaction was then quenched by the addition of 2 mL of 10% sodium potassium tartrate
  3. filtrationThe solids were filtered out
  4. additionThe mixture was diluted with 40 mL of ethyl acetate
  5. washwashed with 20 mL of brine
  6. dry with materialdried over sodium sulfate
  7. filtrationFiltered
  8. concentrationconcentrated
  9. customthe residue was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-016(Waters))
  10. waitmobile phase, water with 0.03% NH4CO3 and CH3CN (10% CH3CN up to 29% in 13 min)
  11. customThis resulted in 25 mg (20%) of 8-Fluoro-9-(1-hydroxy-3-hydroxymethyl-cyclobutylethynyl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a white solid

Sources & evidence

ORD record
ord-eb6f89534e5940399203263a3f169a88
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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