(S)-2-((tert-Butoxycarbonyl)amino)-4,4-dimethylpentanoic acid → (1r,2s)-1-{[(2s,4r)-1-[(1S)-1-((1s,2r)-2-hydroxy-indan-1-ylcarbamoyl)-3,3-dimethyl-butylcarbamoyl]-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid

HRID 1822454Notes

Reaction equation

HRID 1822454 reaction equation
C(O[C:6]([NH:8][C@@H:9]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C:10]([OH:12])=O)=[O:7])(C)(C)C.C(OC(NC(C(C)(C)C)C(O)=O)=O)(C)(C)C.[NH2:34][C@H:35]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH2:37][C@H:36]1[OH:44].C(OC(=O)NC(C(=O)NC1C2C(=CC=CC=2)CC1O)C(C)(C)C)(C)(C)C.ClNC(=O)[O-].C([O:78][C:79]([C:81]1([NH:86][C:87]([CH:89]2[CH2:93][CH:92]([O:94][C:95]3[C:104]4[C:99](=[CH:100][C:101]([O:105][CH3:106])=[CH:102][CH:103]=4)[N:98]=[C:97]([C:107]4[CH:112]=[CH:111][CH:110]=[CH:109][CH:108]=4)[CH:96]=3)[CH2:91][N:90]2C(=O)NC(C(=O)NC2C3C(=CC=CC=3)CC2O)C(C)(C)C)=[O:88])[CH2:83][CH:82]1[CH:84]=[CH2:85])=[O:80])C>>[OH:44][C@@H:36]1[CH2:37][C:38]2[C:43](=[CH:42][CH:41]=[CH:40][CH:39]=2)[C@@H:35]1[NH:34][C:10]([C@@H:9]([NH:8][C:6]([N:90]1[CH2:91][C@H:92]([O:94][C:95]2[C:104]3[C:99](=[CH:100][C:101]([O:105][CH3:106])=[CH:102][CH:103]=3)[N:98]=[C:97]([C:107]3[CH:112]=[CH:111][CH:110]=[CH:109][CH:108]=3)[CH:96]=2)[CH2:93][C@H:89]1[C:87]([NH:86][C@:81]1([C:79]([OH:80])=[O:78])[CH2:83][C@H:82]1[CH:84]=[CH2:85])=[O:88])=[O:7])[CH2:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12]

Participants

7

Reactant 6

HCID 2755926(S)-2-((tert-Butoxycarbonyl)amino)-4,4-dimethylpentanoic acidHCID 50468592-{[(Tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoic acidHCID 9866743(1S,2R)-(-)-1-Amino-2-indanolHCID 22035886ChlorocarbamateHCID 68488177[1-(2-Hydroxy-indan-1-ylcarbamoyl)-2,2-dimethyl-propyl]-carbamic acid tert.butyl esterHCID 684916281-{[1-[1-(2-Hydroxy-indan-1-ylcarbamoyl)-2,2-dimethyl-propylcarbamoyl]-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 57892901(1r,2s)-1-{[(2s,4r)-1-[(1S)-1-((1s,2r)-2-hydroxy-indan-1-ylcarbamoyl)-3,3-dimethyl-butylcarbamoyl]-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acidYield 30%

Procedure

(2S)-tert-butoxycarbonylamino-4,4-dimethylpentanoic acid was attached to the resin as described for the preparation of compound 16 followed by reaction with (1S,2R)-1-amino-2-indanol as described for the preparation of 17 and removal of the Boc group as described for 18. The afforded compound was then reacted with the chlorocarbamate achieved from 12 as described for the preparation of 13 which, after purification by HPLC, gave the title compound (14.2 mg, 30% yield), Purity by HPLC >95% M+H+776.3.

Workup

  1. customafter purification by HPLC

Sources & evidence

ORD record
ord-c31d6631214143efbb339cd36e74edad
Source dataset
uspto-grants-2009_10
Patent number
US07608590B2

Reaction notes

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