Dimethylamine → HCID 22811052, compound

HRID 1492096Notes

Reaction equation

HRID 1492096 reaction equation
[OH:1][C@H:2]1[CH2:33][CH2:32][C@@:31]2([CH3:34])[C@@H:4]([CH2:5][CH2:6][C:7]3[C@@H:30]2[CH2:29][CH2:28][C@@:27]2([CH3:35])[C:8]=3[C:9](=[O:36])[CH2:10][C@@H:11]2[C@H:12]([CH3:26])[CH2:13][CH2:14][CH2:15][C:16](F)([C:21](F)(F)F)[C:17](F)(F)F)[CH2:3]1.[CH3:37][NH:38][CH3:39]>C(O[C@H]1CC[C@@]2(C)[C@@H](CCC3[C@@H]2CC[C@@]2(C)C=3C(=O)C[C@@H]2[C@H](C)CCCO)C1)(=O)C>[CH3:21][CH:16]([CH2:15][CH2:14][CH2:13][C@H:12]([C@@H:11]1[C@:27]2([CH3:35])[C:8](=[C:7]3[C@H:30]([CH2:29][CH2:28]2)[C@:31]2([CH3:34])[CH:4]([CH2:3][CH2:2][CH2:33][CH2:32]2)[CH2:5][CH2:6]3)[C:9](=[O:36])[CH2:10]1)[CH3:26])[CH3:17].[OH:1][C@H:2]1[CH2:33][CH2:32][C@@:31]2([CH3:34])[C@@H:4]([CH2:5][CH2:6][C:7]3[C@@H:30]2[CH2:29][CH2:28][C@@:27]2([CH3:35])[C:8]=3[C:9](=[O:36])[CH2:10][C@@H:11]2[C@H:12]([CH3:26])[CH2:13][CH2:14][CH:15]([N:38]([CH3:39])[CH3:37])[CH:16]([CH3:21])[CH3:17])[CH2:3]1

Participants

5

Reactant 2

HCID 674DimethylamineHCID 13296225,26,26,26,27,27,27-Heptafluoro-3-hydroxycholest-8(14)-en-15-one

Product 2

HCID 22811052HCID 22811052, compoundHCID 67829258HCID 67829258, compound

Reagents, catalysts & solvents 1

HCID 15125792HCID 15125792, compoundSolvent2×

Procedure

The synthetic protocols to be followed for preparing the preferred side chain derivatized cholest-8(14)-en-15-one compounds are known to those of skill in the art. For example, 3β-acetoxy-24-hydroxy-5α-chol-8(14)-en-15-one is converted to 3β-acetoxy-15-keto-5α-chol-8(14)-en-24-oic acid by oxidation of the alcohol with Jones reagent and subsequent hydrolysis of the C-3 acetate. Compounds such as 3β,24-dihydroxy-5α-cholest-8(14)-en-15-one, 3β,25-dihydroxy-5α-cholest-8(14)-en-15-one and 3β-hydroxy-5α-cholesta-8(14),24-dien-15-one arise from a common intermiediate, viz., 3β-acetoxy-15-keto-5α-chol-8(14)en-24-al. The C-24 aldehyde is readily prepared from 3β-acetoxy-24-hydroxy-5α-chol-8(14)-en-15-one by oxidation with periodinane according to the method of Dess and Martin. Wittig olefination of 3β-acetoxy-15-keto-5α-chol-8(14)en-24-al yields a 24-olefin, 3β-acetoxy-5α-cholesta-8(14),24-dien-15-one which may be hydrolyzed to 362 -hydroxy-5α-cholesta-8(14),24-dien-15-one. Hydration of the 3β-acetoxy-5α-cholesta-8(14),24-dien-15-one and hydrolysis of the ester yields either 3β,24-dihydroxy-5α -cholest-8(14)-en-15-one or 3β,25-dihydroxy-5α-cholest-8(14)-en-15-one, depending upon the reaction conditions selected. For example, oxymercuration of the 24-olefin will result in 3β,25-dihydroxy-5α-cholest-8(14)-en-15-one, while hydroboration will give 3β,24-dihydroxy-5α-cholest-8(14)-en-15-one. The 3β-acetoxy-24-hydroxy-5α-chol-8(14)-en-15-one is converted to 3β-acetoxy-5α-chola-8(14),23-dien-15-one by treatment with ortho-nitrophenyl selenocyanate, followed by hydrogen peroxide. Reaction of this 23-olefin with 2-iodoheptafluoropropane produces 3β-acetoxy-23ξ-iodo-25,26,26,26,27,27,27-heptafluoro-5α-cholest-8(14)-en-15-one. Subsequent reduction with tributyl tin hydride and deprotection of the C-3 alcohol yields the F7 analog of the starting sterol, viz., 3β-hydroxy-25,26,26,26,27,27,27-heptafluoro-5α-cholest-8(14)-en-15-one. Alternatively, the free hydroxy in 3β-acetoxy-24-hydroxy-5α-chol-8(14)-en-15-one may be converted to a leaving group and replaced by nucleophilic substitution. Transformation of 3β-acetoxy-24-hydroxy-5α-chol-8(14)-en-15-one to the C-24 tosylate followed by reaction with dimethylamine and saponification gives the 25-aza analog of the cholest-8(14)-en-15-one, 3β-hydroxy-24-dimethylamino-5α-cholest-8(14)-en-15-one.

Sources & evidence

ORD record
ord-ef06447a0c40421f91e5ab638ebf248b
Source dataset
uspto-grants-1994_12
Patent number
US05371077

Reaction notes

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