Ethanol → HCID 53241506, compound

HRID 1879686Notes

Reaction equation

HRID 1879686 reaction equation
[CH:1]1([C:4]2[CH:5]=[CH:6][C:7]3[C:13](=[O:14])[N:12]([C:15]4[CH:22]=[CH:21][CH:20]=[C:19]([C:23]5[CH:28]=[C:27]([NH:29][C:30]6[CH:35]=[CH:34][C:33]([C:36]([N:38]7[CH2:43][CH2:42][O:41][CH2:40][CH2:39]7)=[O:37])=[CH:32][N:31]=6)[C:26](=[O:44])[N:25]([CH3:45])[CH:24]=5)[C:16]=4[CH:17]=[O:18])[CH2:11][CH2:10][NH:9][C:8]=3[CH:46]=2)[CH2:3][CH2:2]1.C(O)C.[BH4-].[Na+]>C1COCC1>[CH:1]1([C:4]2[CH:5]=[CH:6][C:7]3[C:13](=[O:14])[N:12]([C:15]4[CH:22]=[CH:21][CH:20]=[C:19]([C:23]5[CH:28]=[C:27]([NH:29][C:30]6[CH:35]=[CH:34][C:33]([C:36]([N:38]7[CH2:43][CH2:42][O:41][CH2:40][CH2:39]7)=[O:37])=[CH:32][N:31]=6)[C:26](=[O:44])[N:25]([CH3:45])[CH:24]=5)[C:16]=4[CH2:17][OH:18])[CH2:11][CH2:10][NH:9][C:8]=3[CH:46]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 702EthanolHCID 4311764Sodium borohydrideHCID 59548547HCID 59548547, compound

Product 1

HCID 53241506HCID 53241506, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-(8-Cyclopropyl-5-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzaldehyde (350 mg, 0.566 mmol) in 40 mL 1:1 absolute ethanol and THF cooled to 0 C was added sodium borohydride (22 mg, 0.566 mmol, 1 eq) and the reaction was stirred for 1 hour at 0 C. The reaction was quenched with water and 2 drops glacial acetic acid, and stirred for 5 min. The mixture was concentrated in vacuo to remove THF and Ethanol, neutralized with a few drops of aqueous saturated sodium bicarbonate, then concentrated to dryness. The residue was loaded directly on an analogix 40 g column using 10% methanol in CH2Cl2, and eluted with a gradient of 5% to 10% methanol in CH2Cl2 to give a solid. Repurification using HPLC gave 200 mg 8-Cyclopropyl-4-(2-hydroxymethyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one, as a solid, 63% yield.

Workup

  1. temperaturecooled to 0 C
  2. customThe reaction was quenched with water and 2 drops glacial acetic acid
  3. stirringstirred for 5 min
  4. concentrationThe mixture was concentrated in vacuo
  5. customto remove THF and Ethanol
  6. concentrationconcentrated to dryness
  7. washeluted with a gradient of 5% to 10% methanol in CH2Cl2
  8. customto give a solid
  9. customRepurification

Sources & evidence

ORD record
ord-10d9efb993aa4e33acc66e2e3712dfbb
Source dataset
uspto-grants-2012_11
Patent number
US08318719B2

Reaction notes

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