Sodium Carbonate → HCID 89907395, compound

HRID 525651Notes

Reaction equation

HRID 525651 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:26](B3OC(C)(C)C(C)(C)O3)=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)=[O:12])=[CH:9][N:8]=2)[CH2:3]1.Br[C:37]1[S:41][CH:40]=[N:39][CH:38]=1.C([O-])([O-])=O.[Na+].[Na+]>O>[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:26]([C:37]3[S:41][CH:40]=[N:39][CH:38]=3)=[CH:25][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:22])([F:23])[F:24])=[CH:16][CH:15]=3)=[O:12])=[CH:9][N:8]=2)[CH2:3]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 5460595-Bromothiazole2×HCID 89908040HCID 89908040, compound

Product 1

HCID 89907395HCID 89907395, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

(R)-6-(3-Hydroxypyrrolidin-1-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 9.1, 60 mg, 0.122 mmol), 5-bromothiazole (29.9 mg, 0.182 mmol), PdCl2(dppf)-(CH2Cl2) (9.93 mg, 0.012 mmol), Na2CO3 (38.7 mg, 0.365 mmol) DME (627 μL) and water (111 μL) were added to a MW vial, which was sealed, evacuated/purged with argon and was subjected to MW irradiation at 125° C. for 10 min. Additional 5-bromothiazole, (29.9 mg, 0.182 mmol) was added MW irradiation was continued at 125° C. for 10 min. The RM was stirred with Si-Thiol (1.27 mmol/g, 47.9 mg, 0.061 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 9, 25% for 0.2 min then 25% to 55% in 14 min) to afford the title compound as a white solid. UPLC-MS (Condition 1) tR=2.17 min, m/z=451.0-452.0 [M+H]+, m/z=449.0-450.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.70-1.79 (m, 1H) 1.80-1.91 (m, 1H) 3.00 (d, J=11.49 Hz, 1H) 3.25-3.31 (m, 2H) 3.42-3.51 (m, 1H) 4.19-4.25 (m, 1H) 4.74-4.99 (m, 1H) 7.34 (d, J=8.56 Hz, 2H) 7.82-7.88 (m, 2H) 7.91 (s, 1H) 8.08 (d, J=2.45 Hz, 1H) 8.78 (d, J=2.45 Hz, 1H) 9.19 (s, 1H), 10.19 (s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon
  3. customwas subjected to MW irradiation at 125° C. for 10 min
  4. filtrationfiltered
  5. customthe filtrate was evaporated off under reduced pressure
  6. customto give a residue which
  7. customwas purified by preparative HPLC (Condition 9, 25% for 0.2 min

Sources & evidence

ORD record
ord-2d23e9a845f04ee299ab566a1b9958ca
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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