Diisopropylethylamine → (1-{1-[4-Cyclopentyl-6-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester

HRID 1949627Notes

Reaction equation

HRID 1949627 reaction equation
[C:1]([N:11]([CH3:17])[C@H:12]([C:14]([OH:16])=O)[CH3:13])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O: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.[NH2:51][CH:52]([C:78]([CH3:81])([CH3:80])[CH3:79])[C:53]([N:55]1[CH2:59][CH2:58][CH:57]2[N:60]([CH:73]3[CH2:77][CH2:76][CH2:75][CH2:74]3)[CH2:61][CH:62]([C:63]3[C:71]4[C:66](=[CH:67][C:68]([F:72])=[CH:69][CH:70]=4)[NH:65][CH:64]=3)[CH:56]12)=[O:54]>CN1C(=O)CCC1.CCOC(C)=O>[CH2:4]([O:3][C:1](=[O:2])[N:11]([CH:12]([C:14](=[O:16])[NH:51][CH:52]([C:53]([N:55]1[CH2:59][CH2:58][CH:57]2[N:60]([CH:73]3[CH2:77][CH2:76][CH2:75][CH2:74]3)[CH2:61][CH:62]([C:63]3[C:71]4[C:66](=[CH:67][C:68]([F:72])=[CH:69][CH:70]=4)[NH:65][CH:64]=3)[CH:56]12)=[O:54])[C:78]([CH3:81])([CH3:80])[CH3:79])[CH3:13])[CH3:17])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 7016365Z-N-Me-Ala-OHHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 674083852-Amino-1-[4-cyclopentyl-6-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-3,3-dimethyl-butan-1-one

Product 1

HCID 67408704(1-{1-[4-Cyclopentyl-6-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid benzyl ester

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution containing Cbz-N(Me)Ala-OH (116 mg, 0.5 mmol) in anhydrous NMP (5 mL) was cooled to 0° C. HATU (191 mg, 0.5 mmol) and DIPEA (148 mg, 0.7 mmol) were added followed by the addition of crude 39 (218 mg, 0.5 mmol) in anhydrous NMP (5 mL). The reaction mixture was slowly warmed to ambient temperature. After 3 h, the reaction mixture was diluted with EtOAc and washed successively with aqueous NaHCO3 and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 300 mg of crude 40 as an amber-colored oil which was used without further purification. Mass spectrum, m/z [646.4] (M+H)+.

Workup

  1. temperatureThe reaction mixture was slowly warmed to ambient temperature
  2. washwashed successively with aqueous NaHCO3 and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-4864e7574fc1447ba38a0773498fae1d
Source dataset
uspto-grants-2013_03
Patent number
US08399683B2

Reaction notes

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