Diisopropylethylamine → N1-((1R,2S)-1-hydroxy-3-phenyl-1-((2R,4R)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-5-(oxazol-2-yl)-N3,N3-dipropylisophthalamide

HRID 20973Notes

Reaction equation

HRID 20973 reaction equation
C(NC1C=C(C=C(C2OC=CN=2)C=1)[C:13]([NH:15][C@@H:16]([CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C@@H:17]([C@H:26]1[CH2:30][C@@H:29]([S:31]([CH2:34][CH2:35][CH3:36])(=[O:33])=[O:32])[CH2:28][N:27]1C(OC(C)(C)C)=O)[O:18][Si](C(C)(C)C)(C)C)=[O:14])(=O)C1C=CC=CC=1.[CH2:59]([N:62]([CH2:79][CH2:80][CH3:81])[C:63]([C:65]1[CH:66]=[C:67]([CH:71]=[C:72]([C:74]2[O:75][CH:76]=[CH:77][N:78]=2)[CH:73]=1)C(O)=O)=[O:64])[CH2:60][CH3:61].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Si](O[C@H]([C@H]1CC(O)(C2C=CC=CC=2)CN1C(OC(C)(C)C)=O)[C@@H](NC(=O)C1C=CC=C(C(=O)N)C=1)CC1C=C(F)C=C(F)C=1)(C(C)(C)C)(C)C>C(Cl)Cl>[OH:18][C@H:17]([C@H:26]1[CH2:30][C@@H:29]([S:31]([CH2:34][CH2:35][CH3:36])(=[O:33])=[O:32])[CH2:28][NH:27]1)[C@@H:16]([NH:15][C:13](=[O:14])[C:67]1[CH:71]=[C:72]([C:74]2[O:75][CH:76]=[CH:77][N:78]=2)[CH:73]=[C:65]([C:63]([N:62]([CH2:59][CH2:60][CH3:61])[CH2:79][CH2:80][CH3:81])=[O:64])[CH:66]=1)[CH2:44][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210628933-(Dipropylcarbamoyl)-5-(oxazol-2-yl)benzoic acidHCID 67316005(2r,4r)-Tert-butyl 2-((1s,2s)-2-(3-(benzamido)-5-(oxazol-2-yl)benzamido)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylateHCID 68558510(2R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-2-(3-(carbamoyl)benzamido)-3-(3,5-difluorophenyl)propyl)-4-hydroxy-4-phenylpyrrolidine-1-carboxylate

Product 1

HCID 11848640N1-((1R,2S)-1-hydroxy-3-phenyl-1-((2R,4R)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-5-(oxazol-2-yl)-N3,N3-dipropylisophthalamideYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Step 17 (F): (2R,4R)-tert-butyl 2-((1S,2S)-2-(3-(benzamido)-5-(oxazol-2-yl)benzamido)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylate. To a solution of 3-(dipropylcarbamoyl)-5-(oxazol-2-yl)benzoic acid (prepared as reported in WO 2002/02512, 20 mg, 0.062 mmol) in DCM is added HATU (28 mg, 0.073 mmol) and DIEA (33 mg, 0.26 mmol). After the solution is stirred at rt for 5 min, a 28 mg portion of the compounds of step 17 (E) (0.052 mmol) is added. The reaction solution was stirred 16 h at rt, and then the reaction solution was partitioned between ethyl acetate and water, the organic layer was concentrated, and the crude product was purified by chromatography eluting with a step gradient of 20% to 50% to 70% ethyl acetate in hexanes to provide 40 mg (98%) of the desired amide. MS (ESI) (M+H−Boc)+=739.34

Workup

  1. stirringThe reaction solution was stirred 16 h at rt
  2. customthe reaction solution was partitioned between ethyl acetate and water
  3. concentrationthe organic layer was concentrated
  4. customthe crude product was purified by chromatography
  5. washeluting with a step gradient of 20% to 50% to 70% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-6fc5872b93c44e389775cf756b3dc754
Source dataset
uspto-grants-2010_06
Patent number
US07745470B2

Reaction notes

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