Potassium Phosphate, Tribasic → HCID 118045247, compound

HRID 525663Notes

Reaction equation

HRID 525663 reaction equation
[OH:1][C@@H:2]1[C@@H:6]([CH2:7][OH:8])[CH2:5][N:4]([C:9]2[C:28](B3OC(C)(C)C(C)(C)O3)=[CH:27][C:12]([C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=3)=[O:14])=[CH:11][N:10]=2)[CH2:3]1.Br[C:39]1[S:43][CH:42]=[N:41][CH:40]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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>[OH:1][C@H:2]1[C@H:6]([CH2:7][OH:8])[CH2:5][N:4]([C:9]2[C:28]([C:39]3[S:43][CH:42]=[N:41][CH:40]=3)=[CH:27][C:12]([C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:24])[F:25])=[CH:18][CH:17]=3)=[O:14])=[CH:11][N:10]=2)[CH2:3]1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 5460595-BromothiazoleHCID 89908063HCID 89908063, compound

Product 1

HCID 118045247HCID 118045247, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

6-((3R,4R)-3-Hydroxy-4-(hydroxymethyl)pyrrolidin-1-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 17.1, 50 mg, 0.096 mmol), 5-bromothiazole (78 mg, 0.478 mmol), Pd(Ph3P)4 (11.04 mg, 9.55 μmol), K3PO4 (81 mg, 0.382 mmol) toluene (478 μL) were added to a MW vial, which was sealed, evacuated/purged with argon and the RM was stirred for 16 h at 110° C. The RM was diluted with DME (2 mL)/EtOAc (1 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 39.8 mg, 0.057 mmol), centrifuged, the supernatant was filtered and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative SFC (Column Diol, isocratic at 30% in 8 min) to afford the title compound as an amber wax. UPLC-MS (Condition 3) tR=0.90 min, m/z=481.3 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.05-2.15 (m, 1H) 2.99 (dd, J=10.79, 3.14 Hz, 1H) 3.18-3.23 (m, 1H) 3.22-3.28 (m, 1H) 3.39 (m, J=5.40 Hz, 2H) 3.52 (dd, J=11.30 Hz, 1H) 3.94-4.03 (m, 1H) 4.66 (t, J=5.27 Hz, 1H) 5.00 (d, J=4.27 Hz, 1H) 7.36 (d, J=8.41 Hz, 2H) 7.83-7.89 (m, 2H) 7.94 (d, J=0.50 Hz, 1H) 8.09 (d, J=2.38 Hz, 1H) 8.78 (d, J=2.38 Hz, 1H) 9.20 (d, J=0.50 Hz, 1H) 10.22 (s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon
  3. additionThe RM was diluted with DME (2 mL)/EtOAc (1 mL)
  4. filtrationthe supernatant was filtered
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give a residue which
  7. customwas purified by preparative SFC (Column Diol, isocratic at 30% in 8 min)

Sources & evidence

ORD record
ord-e571bc40b0fb49ae97da16205a1e8ce1
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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