Propionamide → 5-Methyl-isoxazole-3-carboxylic acid {(R)-1-[9-((1R,2S,3R,4S)-2,3-dihydroxy-4-propionylamino-cyclopentyl)-6-(1-ethyl-propylamino)-9H-purin-2-yl]-pyrrolidin-3-yl}-amide hydrochloride

HRID 1882584Notes

Reaction equation

HRID 1882584 reaction equation
C1([CH:7]([C:45]2C=CC=CC=2)[CH2:8][NH:9][C:10]2[N:18]=[C:17]([N:19]3[CH2:23][CH2:22][C@@H:21]([NH:24][C:25](N[C@@H]4CCNC4)=[O:26])[CH2:20]3)[N:16]=[C:15]3[C:11]=2[N:12]=[CH:13][N:14]3[C@@H:33]2[CH2:37][C@H:36]([NH:38][C:39](=[O:42])CO)[C@@H:35]([OH:43])[C@H:34]2[OH:44])C=CC=CC=1.[Cl:51]C1N=C2C(N=CN2[C@@H:61]2C[C@H:64]([NH:66]C(=O)CO)[C@@H:63](O)[C@H:62]2[OH:72])=C(NCC(C2C=CC=CC=2)C2C=CC=CC=2)N=1.ClC1N=C2[C:92](N=CN2[C@@H]2C[C@H](NC(=O)CC)[C@@H](O)[C@H]2O)=[C:91](NC(CC)CC)N=1.[C:116](OC(=O)N([C@H]1C[C@@H](N2C=NC3C2=NC(Cl)=NC=3Cl)[C@H](O)[C@@H]1O)C(=O)CC)(C)(C)[CH3:117].C(N)(=O)CC.N1CC[C@@H](NC(C2C=C(C)ON=2)=O)C1>>[ClH:51].[OH:44][C@@H:34]1[C@H:35]([OH:43])[C@@H:36]([NH:38][C:39](=[O:42])[CH2:91][CH3:92])[CH2:37][C@H:33]1[N:14]1[CH:13]=[N:12][C:11]2[C:15]1=[N:16][C:17]([N:19]1[CH2:23][CH2:22][C@@H:21]([NH:24][C:25]([C:64]3[CH:63]=[C:62]([CH3:61])[O:72][N:66]=3)=[O:26])[CH2:20]1)=[N:18][C:10]=2[NH:9][CH:8]([CH2:116][CH3:117])[CH2:7][CH3:45]

Participants

7

Reactant 6

HCID 6578PropionamideHCID 11647233N-{(1S,2R,3S,4R)-4-[2-Chloro-6-(1-ethyl-propylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-propionamideHCID 44140426[(1S,2R,3S,4R)-4-(2,6-dichloro-purin-9-yl)-2,3-dihydroxy-cyclopentyl]-propionyl-carbamic acid tert-butyl ester2×HCID 66630791N-((1S,2R,3S,4R)-4-{6-(2,2-Diphenyl-ethylamino)-2-[(R)-3-((R)-3-pyrrolidin-3-ylureido)-pyrrolidin-1-yl]-purin-9-yl}-2,3-dihydroxy-cyclopentyl)-2-hydroxy-acetamideHCID 666308935-methyl-isoxazole-3-carboxylic acid (R)-pyrrolidin-3-ylamide2×HCID 86637575N-{(1S,2R,3S,4R)-4-[2-Chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-2-hydroxy-acetamide

Product 1

HCID 666310405-Methyl-isoxazole-3-carboxylic acid {(R)-1-[9-((1R,2S,3R,4S)-2,3-dihydroxy-4-propionylamino-cyclopentyl)-6-(1-ethyl-propylamino)-9H-purin-2-yl]-pyrrolidin-3-yl}-amide hydrochloride

Procedure

This compound is prepared analogously to N-((1S,2R,3S,4R)-4-{6-(2,2-diphenyl-ethylamino)-2-[(R)-3-((R)-3-pyrrolidin-3-ylureido)-pyrrolidin-1-yl]-purin-9-yl}-2,3-dihydroxy-cyclopentyl)-2-hydroxy-acetamide (Example 15) by replacing N-{(1S,2R,3S,4R)-4-[2-chloro-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-2-hydroxy-acetamide (Intermediate Q) with N-{(1S,2R,3S,4R)-4-[2-Chloro-6-(1-ethyl-propylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-propionamide [prepared from [(1S,2R,3S,4R)-4-(2,6-dichloro-purin-9-yl)-2,3-dihydroxy-cyclopentyl]-propionyl-carbamic acid tert-butyl ester (Intermediate G) and the appropriate amine using a procedure analogous to 2R,3S,4R)-4-{6-[2,2-Bis-(4-hydroxy-phenyl)-ethylamino]-2-chloro-purin-9-yl}-2,3-dihydroxy-cyclopentyl)-propionamide (Example 22 steps 1 and 2)] and by replacing 1,3-di(R)-pyrrolidin-3-yl-urea (Intermediate B) with 5-methyl-isoxazole-3-carboxylic acid (R)-pyrrolidin-3-ylamide (Intermediate P). (MH+ 570.4)

Sources & evidence

ORD record
ord-f1161acfea754f539d00880cb6678d0c
Source dataset
uspto-grants-2012_11
Patent number
US08318750B2

Reaction notes

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