Dichloromethane → (7-Chlorospiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-yl)(2-fluoro-5-methoxyphenyl)methanone

HRID 2204237Notes

Reaction equation

HRID 2204237 reaction equation
Cl[N:2]1[CH2:7][CH2:6][C:5]2([O:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[N:9]3[CH:17]=[CH:18][CH:19]=[C:8]23)[CH2:4][CH2:3]1.[F:20][C:21]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:22]=1[C:23](O)=[O:24].CCN=C=NCCCN(C)C.CCN(CC)CC.C(Cl)[Cl:51]>>[Cl:51][C:14]1[CH:15]=[CH:16][C:10]2[N:9]3[CH:17]=[CH:18][CH:19]=[C:8]3[C:5]3([CH2:6][CH2:7][N:2]([C:23]([C:22]4[CH:26]=[C:27]([O:30][CH3:31])[CH:28]=[CH:29][C:21]=4[F:20])=[O:24])[CH2:3][CH2:4]3)[O:12][C:11]=2[CH:13]=1

Participants

6

Reactant 5

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27745432-Fluoro-5-methoxybenzoic acidHCID 86723300Chlorospiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]

Product 1

HCID 58550967(7-Chlorospiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-yl)(2-fluoro-5-methoxyphenyl)methanone

Procedure

Chlorospiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine] (62 mg, 0.20 mmol), 2-fluoro-5-methoxybenzoic acid (34 mg, 0.20 mmol), EDCI (38 mg, 0.20 mmol), and Et3N (56 μL, 0.40 mmol) were combined in DCM (1 mL) and the mixture was stirred for 6 h. The mixture was diluted with DCM and was washed with 1N HCl, sat. aq. sodium bicarbonate and brine. The organics were dried over sodium sulfate and were evaporated. The crude material was purified by silica gel chromatography eluting with 0-40% ethyl acetate in hexanes to provide (7-chlorospiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-yl)(2-fluoro-5-methoxyphenyl)methanone. ESI-MS m/z calc. 426.1, found 427.5 (M+1)+. Retention time: 2.12 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.26 (d, J=8.4 Hz, 1H), 7.13-7.07 (m, 2H), 7.05-6.96 (m, 2H), 6.94-6.85 (m, 2H), 6.33 (t, J=3.2 Hz, 1H), 6.08-5.98 (m, 1H), 4.69 (d, J=13.1 Hz, 1H), 3.80 (s, 3H), 3.63-3.44 (m, 2H), 3.33 (t, J=12.8 Hz, 1H), 2.19 (d, J=13.8 Hz, 1H), 2.09-1.96 (m, 2H), 1.60 (s, 1H).

Workup

  1. washwas washed with 1N HCl, sat. aq. sodium bicarbonate and brine
  2. dry with materialThe organics were dried over sodium sulfate
  3. customwere evaporated
  4. customThe crude material was purified by silica gel chromatography
  5. washeluting with 0-40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-42be2969d23c416991b59e3f98e8cfb7
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

Loading…