1,4-Diazepan-6-ol → HCID 10228016, compound

HRID 1072075Notes

Reaction equation

HRID 1072075 reaction equation
C1(S([CH2:9][C:10]2[CH:11]=[CH:12][N:13]3[C:18]=2[C:17]([NH:19][C:20]2[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=2)[N:25]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=2)[N:24]=[CH:23]4)=[N:16][CH:15]=[N:14]3)=O)C=CC=CC=1.[NH:37]1[CH2:43][CH:42]([OH:44])[CH2:41][NH:40][CH2:39][CH2:38]1>CS(C)=O.C(Cl)Cl>[F:36][C:32]1[CH:31]=[C:30]([CH:35]=[CH:34][CH:33]=1)[CH2:29][N:25]1[C:26]2[C:22](=[CH:21][C:20]([NH:19][C:17]3[C:18]4=[C:10]([CH2:9][N:37]5[CH2:43][CH:42]([OH:44])[CH2:41][NH:40][CH2:39][CH2:38]5)[CH:11]=[CH:12][N:13]4[N:14]=[CH:15][N:16]=3)=[CH:28][CH:27]=2)[CH:23]=[N:24]1

Participants

5

Reactant 2

HCID 211142751,4-Diazepan-6-olHCID 22390503HCID 22390503, compound

Product 1

HCID 10228016HCID 10228016, compoundYield 62.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of (5-benzenesulfinylmethyl-pyrrolo[2,1-f][1,2,4]triazin-4-yl)-[1-(3-fluoro-benzyl)-1H-indazol-5-yl]-amine (397 mg, 0.8 mmole) and [1,4]diazepan-6-ol (417 mg, 4.5 equiv, Saari et al., J. Org. Chem., 1971, 36, 1711) in dry DMSO (1.5 mL) in a sealed tube was heated at 140° C. for 11 hr. This was diluted with DCM (150 ml), washed with water and dried (Na2SO4). Removal of the solvent followed by radial chromatography (4 mm silica gel plate; gradient elution with DCM containing 0 to 3% of a 2N NH3 solution in MeOH) gave the title compound as a solid (242 mg, 62%), MS: 487 (M+H)+; HPLC Ret Time: 0.96 min (Xterra S7 3.0×50 mm S7 C18 column, 2 min gradient, 5 ml/min). The racemic material could be separated on a Chiralpak AD 4.6×250 mm column, eluting with 0.05% diethylamine in EtOH for 25 min with a flow rate of 0.7 mL/min) The S and R enantiomers had retention times of 16.20 and 18.90 min respectively. The R enantiomer was synthesized as outlined below.

Workup

  1. washwashed with water
  2. dry with materialdried (Na2SO4)
  3. customRemoval of the solvent
  4. washgradient elution with DCM containing 0 to 3% of a 2N NH3 solution in MeOH)

Sources & evidence

ORD record
ord-172bf42307aa4835a0d0ed089692635d
Source dataset
uspto-grants-2005_06
Patent number
US06908916B2

Reaction notes

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