Sodium Carbonate → HCID 67312704, compound

HRID 2179707Notes

Reaction equation

HRID 2179707 reaction equation
Br[C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[CH2:4][NH:5]C(=O)OC(C)(C)C.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[ClH:40].[N:41]12[CH2:48][CH2:47][CH:44]([CH2:45][CH2:46]1)[C@H:43]([NH:49][C:50]([C:52]1[O:53][C:54]3[C:60](Br)=[CH:59][CH:58]=[CH:57][C:55]=3[CH:56]=1)=[O:51])[CH2:42]2.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[ClH:40].[ClH:40].[NH2:5][CH2:4][C:3]1[CH:13]=[CH:14][CH:15]=[CH:16][C:2]=1[C:60]1[C:54]2[O:53][C:52]([C:50]([NH:49][C@H:43]3[CH:44]4[CH2:45][CH2:46][N:41]([CH2:48][CH2:47]4)[CH2:42]3)=[O:51])=[CH:56][C:55]=2[CH:57]=[CH:58][CH:59]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 70183002-Bromo-N-(tert-butoxycarbonyl)benzylamineHCID 67314189HCID 67314189, compound

Product 1

HCID 67312704HCID 67312704, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6228DimethylformamideSolvent

Procedure

500 mg (1.75 mmol) of tert-butyl 2-bromobenzylcarbamate, 512 mg (2.02 mmol) of bis(pinacolato)diboron, 428.7 mg (4.37 mmol) of potassium acetate, 49.2 mg (0.07 mmol) of PdCl2(dppf), 518.4 mg (1.34 mmol) of N-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzofuran-2-carboxamide hydrochloride (free base: Example 31A), 3.36 ml of 2 M sodium carbonate solution and a further 49.2 mg (0.07 mmol) of PdCl2(dppf) in 5 ml of DMF are reacted by general method D. The crude product which has been dried under high vacuum is stirred in 4 ml of a 1:1 mixture of methanol and 4 M hydrogen chloride in dioxane at room temperature for 2 h. The reaction solution is concentrated, and the resulting crude product is purified by preparative HPLC. The product fractions are concentrated and, after addition of a 3:1 mixture of methanol and 1N hydrochloric acid, again concentrated and dried under high vacuum. 121.6 mg (22.4% of theory) of the title compound are obtained.

Workup

  1. dry with materialThe crude product which has been dried under high vacuum
  2. concentrationThe reaction solution is concentrated
  3. customthe resulting crude product is purified by preparative HPLC
  4. concentrationThe product fractions are concentrated
  5. additionafter addition of a 3:1 mixture of methanol and 1N hydrochloric acid
  6. concentrationagain concentrated
  7. customdried under high vacuum

Sources & evidence

ORD record
ord-639723587fda4e499c4fcdc7f29b5b0f
Source dataset
uspto-grants-2015_06
Patent number
US09067931B2

Reaction notes

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