Sodium Bicarbonate → HCID 89501431, compound

HRID 709355Notes

Reaction equation

HRID 709355 reaction equation
[CH3:1][CH:2]([CH3:41])[C@H:3]([NH:36][C:37](=[O:40])[O:38][CH3:39])[C:4](=[O:35])[N:5]1[CH:9]([C:10]2[NH:11][C:12]([C:15]3[CH:20]=[CH:19][C:18](B4OC(C)(C)C(C)(C)O4)=[CH:17][CH:16]=3)=[CH:13][N:14]=2)[CH2:8][C:7]2([CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[CH2:6]1.Br[C:43]1[CH:48]=[CH:47][C:46]([C:49]2[NH:53][C:52]([C@H:54]3[N:59]4[C:60](=[O:71])[C@@H:61]([NH:66][C:67](=[O:70])[O:68][CH3:69])[CH2:62][CH2:63][C:64](=[O:65])[N:58]4[CH2:57][CH2:56][CH2:55]3)=[N:51][CH:50]=2)=[CH:45][CH:44]=1.C(=O)(O)[O-].[Na+]>C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe].C(O)(C)(C)C>[CH3:69][O:68][C:67](=[O:70])[NH:66][C@H:61]1[CH2:62][CH2:63][C:64](=[O:65])[N:58]2[CH2:57][CH2:56][CH2:55][C@@H:54]([C:52]3[NH:53][C:49]([C:46]4[CH:45]=[CH:44][C:43]([C:18]5[CH:17]=[CH:16][C:15]([C:12]6[NH:11][C:10]([CH:9]7[CH2:8][C:7]8([CH2:34][CH2:33][O:32][CH2:31][CH2:30]8)[CH2:6][N:5]7[C:4](=[O:35])[C@@H:3]([NH:36][C:37]([O:38][CH3:39])=[O:40])[CH:2]([CH3:1])[CH3:41])=[N:14][CH:13]=6)=[CH:20][CH:19]=5)=[CH:48][CH:47]=4)=[CH:50][N:51]=3)[N:59]2[C:60]1=[O:71]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 68206222HCID 68206222, compoundHCID 89510258HCID 89510258, compound

Product 1

HCID 89501431HCID 89501431, compoundYield 45.2%

Reagents, catalysts & solvents 2

HCID 178477754HCID 178477754, compoundCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

In a 10 mL seal tube, methyl (2S)-3-methyl-1-oxo-1-(3-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)-8-oxa-2-azaspiro[4.5]decan-2-yl)butan-2-ylcarbamate (45 mg, 79.4 μmol), methyl (4S,7S)-4-(5-(4-bromophenyl)-1H-imidazol-2-yl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate (37.8 mg, 79.4 μmol) and sodium bicarbonate (sat solution, 0.4 ml) were combined with tert-butanol (2.6 ml) to give a light brown suspension and deoxygenated for 5 min. PdCl2(DPPF) (5.81 mg, 7.94 μmol) was added and flushed with nitrogen. It was sealed heating at 90° C. for 4 hr. The reaction mixture was diluted with EtOAc (10 ml), filtered and concentrated in vacuo. The residue was purified on a silica gel column (CH2Cl2, 2%, 3%, 5%, 8% MeOH/CH2Cl2) to afford {(4S,7S)-4-[5(4′-{2-[2-((S)-2-Methoxycarbonylamino-3-methyl-butyryl)-8-oxa-2-aza-spiro[4.5]dec-3-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1H-imidazol-2-yl]-6,10-dioxo-octahydro-pyridazino[1,2-a][1,2]diazepin-7-yl}-carbamic acid methyl ester as a light yellow solid (30 mg, 42.9%). ESI-LRMS m/e calcd for C44H53N9O8, [M+] 835. found 836 [M+H]. 1H NMR (DMSO-d6) δ: 12.09-12.45 (m, 1H), 7.57-7.99 (m, 11H), 7.49 (d, J=8.3 Hz, 2H), 5.80 (br. s., 1H), 4.93-5.16 (m, 1H), 4.46 (d, J=11.3 Hz, 2H), 3.92-4.27 (m, 1H), 3.64 (br. s., 3H), 3.50-3.60 (m, 10H), 2.88 (t, J=10.3 Hz, 1H), 1.77-2.36 (m, 6H), 1.63 (br. s., 2H), 1.48 (d, J=11.5 Hz, 1H), 0.77-1.02 (m, 6H), 0.67 (d, J=6.5 Hz, 2H), 0.12 (d, J=6.8 Hz, 1H).

Workup

  1. customIn a 10 mL seal tube
  2. customto give a light brown suspension
  3. customdeoxygenated for 5 min
  4. customflushed with nitrogen
  5. customIt was sealed
  6. additionThe reaction mixture was diluted with EtOAc (10 ml)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified on a silica gel column (CH2Cl2, 2%, 3%, 5%, 8% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-4bdb108d05914f01acd0bf92a1e1f5c2
Source dataset
uspto-grants-2015_11
Patent number
US09180193B2

Reaction notes

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