1,2-Dimethoxyethane → HCID 118044901, compound

HRID 525650Notes

Reaction equation

HRID 525650 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:38][CH:39]=[CH:40][N:41]=1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>O>[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:26]([C:37]3[S:38][CH:39]=[CH:40][N:41]=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

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 764302-BromothiazoleHCID 89908040HCID 89908040, compound

Product 1

HCID 118044901HCID 118044901, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

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, 50 mg, 0.101 mmol), 2-bromothiazole (24.9 mg, 0.152 mmol), PdCl2(dppf)-(CH2Cl2) (8.28 mg, 10.14 μmol), Na2CO3 (32.2 mg, 0.304 mmol), DME (522 μL) and water (92 μL) were added to a MW vial, which was sealed, evacuated/purged with argon, and RM was stirred at 90° C. for 16 h. The RM was diluted with THF (2 mL), treated with Si-Thiol (1.27 mmol/g, 39.9 mg, 0.051 mmol), filtered and the filtrate was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 9, 40% for 0.2 min then 40% to 70% in 14 min) to yield the title compound as a white solid. UPLC-MS (Condition 1) tR=2.51 min, m/z=451-452 [M+H]+, m/z=449-450 [M−H]; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.71-1.80 (m, 1H) 1.81-1.92 (m, 1H) 2.94 (d, J=11.74 Hz, 1H) 3.25-3.30 (m, 2H) 3.43-3.53 (m, 1H) 4.18-4.26 (m, 1H) 4.81-4.94 (m, 1H) 7.35 (d, J=8.56 Hz, 2H) 7.83-7.88 (m, 2H) 7.89 (d, J=3.42 Hz, 1H) 7.94 (d, J=3.42 Hz, 1H) 8.19 (d, J=2.45 Hz, 1H) 8.82 (d, J=2.20 Hz, 1H) 10.25 (s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon, and RM
  3. additionThe RM was diluted with THF (2 mL)
  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, 40% for 0.2 min

Sources & evidence

ORD record
ord-7b97477bb93d4450b4915e2deac49f17
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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