Sodium Bicarbonate → HCID 67507207, compound

HRID 1751573Notes

Reaction equation

HRID 1751573 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:22]=[C:21]3[C:12]([C:13]4[CH:14]=[CH:15][C:16]([C:23]5[NH:27][C:26]([CH:28]6[CH:33]7[CH2:34][CH:30]([CH2:31][CH2:32]7)[N:29]6[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[N:25][CH:24]=5)=[CH:17][C:18]=4[CH2:19][CH2:20]3)=[CH:11][CH:10]=2)O1.Br[C:44]1[NH:48][C:47]([C@@H:49]2[CH2:53][CH2:52][CH2:51][N:50]2[C:54](=[O:64])[C@@H:55]([NH:59][C:60](=[O:63])[O:61][CH3:62])[CH:56]([CH3:58])[CH3:57])=[N:46][CH:45]=1.C([O-])(O)=O.[Na+]>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.COCCOC>[CH3:62][O:61][C:60]([NH:59][C@@H:55]([CH:56]([CH3:58])[CH3:57])[C:54]([N:50]1[CH2:51][CH2:52][CH2:53][C@H:49]1[C:47]1[NH:48][C:44]([C:9]2[CH:22]=[C:21]3[C:12]([C:13]4[CH:18]=[CH:17][C:16]([C:23]5[NH:27][C:26]([C@@H:28]6[C@@H:33]7[CH2:34][C@@H:30]([CH2:31][CH2:32]7)[N:29]6[C:35]([O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[O:36])=[N:25][CH:24]=5)=[CH:15][C:14]=4[CH2:19][CH2:20]3)=[CH:11][CH:10]=2)=[CH:45][N:46]=1)=[O:64])=[O:63]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 56605304methyl ((S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamateHCID 86708777HCID 86708777, compound

Product 1

HCID 67507207HCID 67507207, compoundYield 88.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

To 1R,3S,4S)-tert-butyl 3-(5-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,10-dihydrophenanthren-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (97 mg, 0.17 mmol), methyl (S)-1-((S)-2-(5-bromo-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (67 mg, 0.18 mmol), Pd(PPh3)4 (10 mg, 0.009 mmol). DME (1.7 mL) was added and followed by 0.7 mL 1M NaHCO3 aqueous solution. The reaction was purged with Ar and heated to 120° C. at microwave synthesizer for 0.5 hour. The reaction was cooled to room temperature and concentrated down. EtOAc was added and washed with sat. NaHCO3 aqueous (2×) and sat. NaCl aqueous (1×). The organic layer was concentrated down after drying over sodium sulfate and subject to silica gel chromatography with an eluent of ethyl acetate and hexane at a gradient of 40-100% with an ISCO column (12 g silica gel). The fractions containing product were combined and the solvent was removed under reduced pressure to provide (1R,3S,4S)-tert-butyl 3-(5-(7-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-9,10-dihydrophenanthren-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (110 mg, 88%). MS (ESI) m/z 734 [M+H]+.

Workup

  1. customThe reaction was purged with Ar
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated down
  4. additionEtOAc was added
  5. washwashed with sat. NaHCO3 aqueous (2×) and sat. NaCl aqueous (1×)
  6. concentrationThe organic layer was concentrated down
  7. dry with materialafter drying over sodium sulfate
  8. additionThe fractions containing product
  9. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-8e2d40fbf3134a36b56df74f8114b09c
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

Loading…