4-Amino-2-hydroxybutanoic acid → HCID 118045114, compound

HRID 525775Notes

Reaction equation

HRID 525775 reaction equation
Cl[C:2]1[C:21]([C:22]2[NH:26][N:25]=[CH:24][CH:23]=2)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([Cl:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.[NH2:27][CH2:28][CH2:29][CH:30]([OH:34])[C:31]([OH:33])=[O:32].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN1C(=O)CCC1>[Cl:19][C:16]([F:18])([F:17])[O:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6]([C:5]2[CH:20]=[C:21]([C:22]3[NH:26][N:25]=[CH:24][CH:23]=3)[C:2]([NH:27][CH2:28][CH2:29][CH:30]([OH:34])[C:31]([OH:33])=[O:32])=[N:3][CH:4]=2)=[O:7])=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 260624-Amino-2-hydroxybutanoic acidHCID 62657Potassium Phosphate, TribasicHCID 722015896-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide

Product 1

HCID 118045114HCID 118045114, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
170 °C

Procedure

6-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide (Stage 48.1, 20 mg, 0.05 mmol), 4-amino-2-hydroxybutanoic acid (23.4 mg, 0.200 mmol), K3PO4 (106 mg, 0.501 mmol) and NMP (0.4 mL) were added to a MW vial, which was sealed, flushed with argon and stirred at 170° C. for 1 h. The RM was filtered and the residue washed with NMP. The combined organic phases were acidified with TFA, diluted with water and MeCN, filtered and purified by preparative HPLC (Condition 11—gradient to 50% B in 7 min). The MeCN was evaporated off under reduced pressure to give an aqueous solution which was left for 2 days at 4° C. The resulting precipitate was filtered, washed with water and dried to afford the title compound as a white solid. UPLC-MS (Condition 8) tR=0.93 min, m/z=482.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.73-1.91 (m, 1H) 1.99-2.17 (m, 1H) 3.58-3.82 (m, 2H) 4.07 (s, 1H) 5.22-5.50 (m, 1H) 6.97 (s, 1H) 7.36 (d, J=8.44 Hz, 2H) 7.89 (d, J=8.80 Hz, 2H) 7.95 (s, 1H) 8.42 (s, 1H) 8.68 (s, 1H) 8.91 (br. s, 1H) 10.23 (s, 1H) 12.47 (br. s, 1H) 13.19 (br. s, 1H).

Workup

  1. customwas sealed
  2. customflushed with argon
  3. filtrationThe RM was filtered
  4. washthe residue washed with NMP
  5. additiondiluted with water and MeCN
  6. filtrationfiltered
  7. custompurified by preparative HPLC (Condition 11—gradient to 50% B in 7 min)
  8. customThe MeCN was evaporated off under reduced pressure
  9. customto give an aqueous solution which
  10. waitwas left for 2 days at 4° C
  11. filtrationThe resulting precipitate was filtered
  12. washwashed with water
  13. customdried

Sources & evidence

ORD record
ord-e90255a561034478ae0a576475f35b1b
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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