Diisopropylethylamine → [(S)-((S)-1-{(5R,8S)-10,10-Dimethyl-8-[(1R,2S)-1-(pyrrolidine-1-sulfonylaminocarbonyl)-2-vinyl-cyclopropylcarbamoyl]-7-aza-dispiro[3.0.4.1]decane-7-carbonyl}-2,2-dimethyl-propylcarbamoyl)-(1-methyl-cyclohexyl)-methyl]-carbamic acid tert-butyl ester

HRID 77257Notes

Reaction equation

HRID 77257 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:13]1([CH3:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].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.[N:53]1([S:58]([NH:61][C:62]([C@@:64]2([NH:69][C:70]([C@@H:72]3[CH2:83][C@:75]4([C:80]([CH3:82])([CH3:81])[C:76]54[CH2:79][CH2:78][CH2:77]5)[CH2:74][N:73]3[C:84](=[O:91])[C@@H:85]([NH2:90])[C:86]([CH3:89])([CH3:88])[CH3:87])=[O:71])[CH2:66][C@H:65]2[CH:67]=[CH2:68])=[O:63])(=[O:60])=[O:59])[CH2:57][CH2:56][CH2:55][CH2:54]1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:10](=[O:12])[NH:90][C@H:85]([C:84]([N:73]1[C@H:72]([C:70](=[O:71])[NH:69][C@:64]2([C:62]([NH:61][S:58]([N:53]3[CH2:54][CH2:55][CH2:56][CH2:57]3)(=[O:60])=[O:59])=[O:63])[CH2:66][C@H:65]2[CH:67]=[CH2:68])[CH2:83][C@:75]2([C:80]([CH3:82])([CH3:81])[C:76]32[CH2:79][CH2:78][CH2:77]3)[CH2:74]1)=[O:91])[C:86]([CH3:89])([CH3:88])[CH3:87])[C:13]1([CH3:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57785383(2S)-2-(tert-butoxycarbonylamino)-2-(1-methylcyclohexyl)acetic acidHCID 59533294(5R,8S)-7-((S)-2-Amino-3,3-dimethyl-butyryl)-10,10-dimethyl-7-aza-dispiro[3.0.4.1]decane-8-carboxylic acid [(1R,2S)-1-(pyrrolidine-1-sulfonylaminocarbonyl)-2-vinyl-cyclopropyl]-amide

Product 1

HCID 59533192[(S)-((S)-1-{(5R,8S)-10,10-Dimethyl-8-[(1R,2S)-1-(pyrrolidine-1-sulfonylaminocarbonyl)-2-vinyl-cyclopropylcarbamoyl]-7-aza-dispiro[3.0.4.1]decane-7-carbonyl}-2,2-dimethyl-propylcarbamoyl)-(1-methyl-cyclohexyl)-methyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of (S)-tert-Butoxycarbonylamino-(1-methyl-cyclohexyl)-acetic acid (0.217 g; 0.80 mmol) (prepared according to Tetrahedron Let. 2007, 48, 6343-6347) and HATU (0.38 g; 1.00 mmol) in DCM (10 mL) was stirred for 20 min at ambient temperature. After addition of DIPEA (0.698 mL; 4.00 mmol) and (5R,8S)-7-((S)-2-Amino-3,3-dimethyl-butyryl)-10,10-dimethyl-7-aza-dispiro[3.0.4.1]decane-8-carboxylic acid [(1R,2S)-1-(pyrrolidine-1-sulfonylaminocarbonyl)-2-vinyl-cyclopropyl]-amide (0.400 g; 0.67 mmol) in DCM (10 mL) the reaction mixture was stirred for 15 h, the solvent was removed in vacuo and the residue was purified by preparative HPLC (method L) to yield the title compound. LC-MS (method E): Rt=2.91 min; M/z=818 [M+H], HPLC (method A3) Rt=7.18 min

Workup

  1. customthe solvent was removed in vacuo
  2. customthe residue was purified by preparative HPLC (method L)

Sources & evidence

ORD record
ord-471387ad9d364c0ebad4ef16939e26de
Source dataset
uspto-grants-2014_09
Patent number
US08840878B2

Reaction notes

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