Acetic Anhydride → HCID 118195207, compound

HRID 924027Notes

Reaction equation

HRID 924027 reaction equation
[NH2:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[C:27]([C:28]3[CH:29]=[N:30][CH:31]=[N:32][CH:33]=3)=[CH:26][C:11]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]([Cl:25])([F:24])[F:23])=[CH:17][CH:16]=3)=[O:13])=[CH:10][N:9]=2)[CH2:4]1.[C:34](OC(=O)C)(=[O:36])[CH3:35].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[C:34]([NH:1][CH2:2][C@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[C:27]([C:28]3[CH:33]=[N:32][CH:31]=[N:30][CH:29]=3)=[CH:26][C:11]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]([Cl:25])([F:23])[F:24])=[CH:17][CH:16]=3)=[O:13])=[CH:10][N:9]=2)[CH2:4]1)(=[O:36])[CH3:35]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 10340Sodium CarbonateHCID 89906864HCID 89906864, compound

Product 1

HCID 118195207HCID 118195207, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

(S)-6-(3-(Aminomethyl)pyrrolidin-1-yl)-N-(4-(chlorodifluoromethoxy)phenyl)-5-(pyrimidin-5-yl)nicotinamide (Example 177, 30 mg, 0.063 mmol) was dissolved in dioxane (0.5 mL), acetic anhydride (7.09 mg, 0.069 mmol) was added and the RM was stirred for 3 h at RT. The RM was poured into 15 mL of Na2CO3 10%, then extracted with EtOAc. The combined organic layers were dried over Na2SO4 and evaporated to dryness under reduced pressure, dissolved in MeOH, evaporated and dried under HV to afford the title compound as an off-white solid. HPLC (Condition 4) tR=4.95 min, UPLC-MS (Condition 3) tR=0.93 min, m/z=517.3 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.44-1.60 (m, 1H) 1.75 (s, 3H) 1.79-1.93 (m, 1H) 2.15-2.31 (m, 1H) 2.86-3.02 (m, 3H) 3.04-3.20 (m, 2H) 3.23-3.36 (m, 1H) 7.33 (d, J=8.21 Hz, 2H) 7.77-7.93 (m, 3H) 8.08 (d, J=2.35 Hz, 1H) 8.77 (d, J=0.78 Hz, 1H) 8.87 (s, 2H) 9.17 (s, 1H) 10.16 (s, 1H).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. customevaporated to dryness under reduced pressure
  4. dissolutiondissolved in MeOH
  5. customevaporated
  6. customdried under HV

Sources & evidence

ORD record
ord-cbc5dabe1af14de084f4c30b11d5f8be
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

Loading…