Diisopropylethylamine → HCID 69675260, compound

HRID 1751712Notes

Reaction equation

HRID 1751712 reaction equation
[CH3:1][C@@H:2]1[CH2:6][NH:5][C@H:4]([C:7]2[NH:8][C:9]([C:12]3[CH:13]=[C:14]4[CH2:27][O:26][C:25]5[C:16]6=[C:17]([CH:22]=[C:23]([C:28]7[NH:32][C:31]([C@@H:33]8[CH2:37][C@H:36]([CH3:38])[CH2:35][NH:34]8)=[N:30][CH:29]=7)[CH:24]=5)[CH2:18][O:19][C:20]([CH:21]=3)=[C:15]46)=[CH:10][N:11]=2)[CH2:3]1.[CH3:39][O:40][C:41]([NH:43][C@@H:44]([CH:48]([CH3:50])[CH3:49])[C:45](O)=[O:46])=[O:42].[C:51]([O:55][C:56]([NH:58][C@H:59]([C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[C:60]([OH:62])=O)=[O:57])([CH3:54])([CH3:53])[CH3:52].CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:39][O:40][C:41]([NH:43][C@@H:44]([CH:48]([CH3:50])[CH3:49])[C:45]([N:34]1[CH2:35][C@@H:36]([CH3:38])[CH2:37][C@H:33]1[C:31]1[NH:32][C:28]([C:23]2[CH:22]=[C:17]3[CH2:18][O:19][C:20]4[C:15]5=[C:14]([CH:13]=[C:12]([C:9]6[NH:8][C:7]([C@@H:4]7[CH2:3][C@H:2]([CH3:1])[CH2:6][N:5]7[C:60](=[O:62])[C@H:59]([NH:58][C:56]([O:55][C:51]([CH3:52])([CH3:53])[CH3:54])=[O:57])[C:63]7[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=7)=[N:11][CH:10]=6)[CH:21]=4)[CH2:27][O:26][C:25]([CH:24]=2)=[C:16]35)=[CH:29][N:30]=1)=[O:46])=[O:42]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 2755953(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acidHCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 69675388HCID 69675388, compoundHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate

Product 1

HCID 69675260HCID 69675260, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2,7-bis(2-((2S,4S)-4-methylpyrrolidin-2-yl)-1H-imidazol-5-yl)-5,10-dihydrochromeno[5,4,3-cde]chromene was obtained as in Example OY. A mixture of (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (124 mg, 0.706 mmol), (R)-2-(tert-butoxycarbonylamino)-2-phenylacetic acid (177 mg, 0.706 mmol), COMU (665 mg, 1.55 mmol) in 3.7 mL DMF was allowed to preactivate for 20 minutes before it was added to 449 mg of the crude amine in 3.7 mL DMF with 0.74 mL DIPEA. Once starting material was consumed, by LCMS monitoring, the reaction mixture was neutralized with formic acid, diluted with methanol and purified by reverse phase HPLC three products, two homodimers and the heterodimer (S)-2-(methoxycarbonylamino)-1-((2S,4S)-2-(5-(7-(2-((2S,4S)-1-((R)-2-(t-butoxycarbonylamino)-2-phenylacetyl)-4-methylpyrrolidin-2-yl)-1H-imidazol-5-yl)-5,10-dihydrochromeno[5,4,3-cde]chromen-2-yl)-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl)-3-methylbutan-1-one as the trifluoroacetate salts. The eluted fractions were concentrated under reduced pressure, basified with saturated sodium bicarbonate solution and extracted into dichloromethane. Concentration under reduced pressure gave product (86 mg).

Workup

  1. customOnce starting material was consumed, by LCMS monitoring
  2. additiondiluted with methanol
  3. custompurified by reverse phase HPLC three products, two homodimers
  4. concentrationThe eluted fractions were concentrated under reduced pressure
  5. extractionextracted into dichloromethane
  6. concentrationConcentration under reduced pressure

Sources & evidence

ORD record
ord-8693963a27fe492fae540ad814b07972
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

Loading…