Dichloromethane → HCID 118080102, compound

HRID 1485764Notes

Reaction equation

HRID 1485764 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[N:16][N:17]([CH:19]4[CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20]4)[CH:18]=3)=[CH:11][CH:12]=2)[N:7]([C:30]([O-:32])=O)[CH2:6][C@@H:5]1[CH3:33])(=[O:3])[CH3:2].F[C:35]([F:40])([F:39])[C:36](O)=O.[C:41](=[O:44])([O-])[O-].[K+].[K+].Cl[CH2:48]Cl>>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[N:16][N:17]([CH:19]4[CH2:22][NH:21][CH2:20]4)[CH:18]=3)=[CH:11][CH:12]=2)[N:7]([C:30]([O:44][CH:41]2[CH2:48][C:35]([F:40])([F:39])[CH2:36]2)=[O:32])[CH2:6][C@@H:5]1[CH3:33])(=[O:3])[CH3:2]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 131736754HCID 131736754, compound

Product 1

HCID 118080102HCID 118080102, compound

Procedure

A 100-mL round-bottom flask was charged with (S)-4-acetyl-7-(1-(1-(tert-butoxycarbonyl)azetidin-3-yl)-1H-pyrazol-4-yl)-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate (300 mg, 0.51 mmol), trifluoroacetic acid (3 mL) and dichloromethane (5 mL). The resulting solution stirred for 1 h at room temperature. The pH of the solution was adjusted to 8 with 2 M aqueous potassium carbonate solution. The resulting mixture was extracted with dichloromethane (3×15 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by Prep-HPLC with the following conditions (Waters I): Column, Xbridge Prep C18 OBD column, Sum, 19×150 mm; mobile phase, Water (0.03% NH4OH) and CH3CN (16% CH3CN up to 34% in 10 min); Detector, UV 220&254 nm. This afforded (S)-3,3-difluorocyclobutyl 4-acetyl-7-(1-(azetidin-3-yl)-1H-pyrazol-4-yl)-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate (40 mg, 16%) of as a yellow solid. 1H NMR (300 MHz, CD3OD) δ ppm 1.16 (d, J=6.90 Hz, 3H), 1.92-2.17 (m, 8H), 2.28 (s, 3H), 3.41-59 (m, 1H), 4.02-4.11 (m, 2H), 4.18-4.32 (m, 3H), 5.03-5.21 (m, 2H), 5.31-5.42 (m, 1H), 7.39-7.51 (m, 2H), 7.94 (s, 1H), 8.07 (s, 1H), 8.19 (s, 1H). MS (ESI, pos. ion) m/z 446 [M+H]+.

Workup

  1. extractionThe resulting mixture was extracted with dichloromethane (3×15 mL)
  2. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by Prep-HPLC with the following conditions (Waters I)
  5. waitmobile phase, Water (0.03% NH4OH) and CH3CN (16% CH3CN up to 34% in 10 min)

Sources & evidence

ORD record
ord-5f289c44a7624c31a599f35596a55045
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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