Dichloromethane → [4-(4-Chloro-7H-Pyrrolo[2,3-d]pyrimidin-6-yl]-phenyl]-methanol

HRID 1295652Notes

Reaction equation

HRID 1295652 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[H-].C([Al+]CC(C)C)C(C)C.ClCCl.C([O:22][C:23](=O)[C:24]1[CH:29]=[CH:28][C:27]([C:30]2[NH:39][C:33]3[N:34]=[CH:35][N:36]=[C:37]([Cl:38])[C:32]=3[CH:31]=2)=[CH:26][CH:25]=1)C>C1COCC1.O1CCOCC1>[Cl:38][C:37]1[C:32]2[CH:31]=[C:30]([C:27]3[CH:26]=[CH:25][C:24]([CH2:23][OH:22])=[CH:29][CH:28]=3)[NH:39][C:33]=2[N:34]=[CH:35][N:36]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 21225700Diisobutylaluminumhydride2×HCID 21226445Aluminium lithium hydrideHCID 232826964-(4-Chloro-7H-pyrrolo[2,3-D]pyrimidin-6-YL)benzoic acid ethyl ester

Product 1

HCID 86595337[4-(4-Chloro-7H-Pyrrolo[2,3-d]pyrimidin-6-yl]-phenyl]-methanol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

The following Examples are synthesized using an analogous procedure as described in Example 1. However, a modified protocol is applied for the preparation of the intermediates: Instead of reducing the ethyl-ester with lithium aluminum hydride in THF (as described in step 1.2), the 4-hydroxymethyl derivatives are prepared by reduction with diisobutyl-aluminium hydride in a 1:1 mixture of dichloromethane and dioxane at ambient temperature (Examples 67-72 and 76-78). For preparing the intermediates of Examples 73-75, reduction of 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-benzoic acid ethyl ester with diisobutyl-aluminium hydride in THF at ambient temperature yields [4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-phenyl]-methanol (see step 108.3). Substitution of the chlorine by 2-methoxy-5-amino-phenol as described in step 1.1 then gives 5-[6-(4-hydroxymethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino]-2-methoxy-phenol.

Workup

  1. customHowever, a modified protocol is applied for the preparation of the intermediates

Sources & evidence

ORD record
ord-49a6f4e314684eed8c36954afa3140c8
Source dataset
uspto-grants-2007_07
Patent number
US07244729B2

Reaction notes

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