Phenyl chloroformate → Trifluoroacetic acid

HRID 2382403Notes

Reaction equation

HRID 2382403 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[NH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[N:22]=[C:21]3[C:17]([N:18]=[CH:19][N:20]3[C@@H:23]3[CH2:27][C@H:26]([NH:28][C:29](=[O:32])[CH2:30][OH:31])[C@@H:25]([OH:33])[C@H:24]3[OH:34])=[C:16]([NH:35][CH2:36][CH:37]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[N:15]=2)[CH2:10]1.Cl[C:51](OC1C=CC=CC=1)=[O:52].[OH:60][C:61]1[CH:62]=[C:63]([CH:66]=[CH:67][CH:68]=1)[CH2:64][NH2:65]>CN1C(=O)CCC1.CO>[C:3]([OH:5])([C:2]([F:7])([F:6])[F:1])=[O:4].[C:44]1([CH:37]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:36][NH:35][C:16]2[N:15]=[C:14]([N:11]3[CH2:12][CH2:13][C@@H:9]([NH:8][C:51]([NH:65][CH2:64][C:63]4[CH:66]=[CH:67][CH:68]=[C:61]([OH:60])[CH:62]=4)=[O:52])[CH2:10]3)[N:22]=[C:21]3[C:17]=2[N:18]=[CH:19][N:20]3[C@@H:23]2[CH2:27][C@H:26]([NH:28][C:29](=[O:32])[CH2:30][OH:31])[C@@H:25]([OH:33])[C@H:24]2[OH:34])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

7

Reactant 3

HCID 15891Phenyl chloroformateHCID 7358943-(Aminomethyl)phenolHCID 42632577N-{(1S,2R,3S,4R)-4-[2-((R)-3-Amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-2-hydroxy-acetamide trifluoroacetate

Product 2

HCID 6422Trifluoroacetic acidHCID 24862888N-[(1S,2R,3S,4R)-4-(6-(2,2-Diphenyl-ethylamino)-2-{(R)-3-[3-(3-hydroxy-benzyl)-ureido]-pyrrolidin-1-yl}-purin-9-yl)-2,3-dihydroxy-cyclopentyl]-2-hydroxy-acetamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of N-{(1S,2R,3S,4R)-4-[2-((R)-3-amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-2-hydroxy-acetamide trifluoroacetate (Example 1) (1.1 g, 2 mmol) in NMP (2 ml) and MeOH (10 ml) is added dropwise phenyl chloroformate (0.47 g, 3 mmol). The reaction mixture is allowed to stir at room temperature for 3 hours and then treated with 3-hydroxybenzylamine (0.55 g, 4.45 mmol) and stirred for a further 2 hours at 80° C. Purification of the product by C-18 reverse phase column chromatography eluting with acetonitrile:water:TFA (0.1%) (gradient of 0 to 100% acetonitrile) yields the title compound. (MH+ 722.31)

Workup

  1. stirringstirred for a further 2 hours at 80° C
  2. customPurification of the product by C-18 reverse phase column chromatography
  3. washeluting with acetonitrile

Sources & evidence

ORD record
ord-7360d37bf03e433bade69c06581b0d73
Source dataset
uspto-grants-2012_09
Patent number
US08258141B2

Reaction notes

Loading…