Potassium Carbonate → HCID 178495671, compound

HRID 1751630Notes

Reaction equation

HRID 1751630 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:31](=[CH:32][CH:33]=1)[C:8]1[NH:9][C:10]([C@@H:12]3[CH2:16][C@H:15]([CH2:17][O:18][CH3:19])[CH2:14][N:13]3[C:20](=[O:30])[C@@H:21]([NH:25][C:26](=[O:29])[O:27][CH3:28])[CH:22]([CH3:24])[CH3:23])=[N:11][C:7]=1[CH:6]=[CH:5]2.[CH3:34][CH:35]([CH3:71])[C@H:36]([NH:66][C:67](=[O:70])[O:68][CH3:69])[C:37](=[O:65])[N:38]1[CH2:42][CH2:41][CH2:40][C@H:39]1[C:43]1[NH:47][C:46]2[C:48]3[C:53]([CH:54]=[CH:55][C:45]=2[N:44]=1)=[CH:52][C:51](B1OC(C)(C)C(C)(C)O1)=[CH:50][CH:49]=3.C([O-])([O-])=O.[K+].[K+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:69][O:68][C:67]([NH:66][C@@H:36]([CH:35]([CH3:71])[CH3:34])[C:37]([N:38]1[CH2:42][CH2:41][CH2:40][C@H:39]1[C:43]1[NH:47][C:46]2[C:48]3[C:53]([CH:54]=[CH:55][C:45]=2[N:44]=1)=[CH:52][C:51]([C:2]1[CH:3]=[C:4]2[C:31](=[CH:32][CH:33]=1)[C:8]1[NH:9][C:10]([C@@H:12]4[CH2:16][C@H:15]([CH2:17][O:18][CH3:19])[CH2:14][N:13]4[C:20](=[O:30])[C@@H:21]([NH:25][C:26](=[O:29])[O:27][CH3:28])[CH:22]([CH3:24])[CH3:23])=[N:11][C:7]=1[CH:6]=[CH:5]2)=[CH:50][CH:49]=3)=[O:65])=[O:70]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 178495669HCID 178495669, compoundHCID 178502307HCID 178502307, compound

Product 1

HCID 178495671HCID 178495671, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

Methyl (S)-1-((2S,4S)-2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (210 mg, 0.406 mmol), methyl (S)-3-methyl-1-oxo-1-((S)-2-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate (253 mg, 0.487 mmol), Pd(PPh3)4 (47 mg, 0.0406 mmol) and K2CO3 (2M in H2O, 0.50 mL, 1.0 mmoL) were combined in DME (4 mL). The mixture was degassed with bubbling N2 for 10 min the heated to 85° C. for 15 h. After cooling, the reaction mixture was diluted with 5 mL MeOH, filtered and concentrated. The crude residue was purified by reverse phase HPLC to afford methyl {(2S)-1-[(2S,4S)-2-{2′-[(2S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}pyrrolidin-2-yl]-1H,1′H-7,7′-binaphtho[1,2-d]imidazol-2-yl}-4-(methoxymethyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate (140 mg, 42%). MS (ESI) m/z 831 [M+H]+.

Workup

  1. customThe mixture was degassed with bubbling N2 for 10 min the
  2. temperatureAfter cooling
  3. additionthe reaction mixture was diluted with 5 mL MeOH
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-6e4dd43f1dd548bea5bd67f99f1c1612
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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