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

HRID 1908143Notes

Reaction equation

HRID 1908143 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:15]3[CH:16]=[CH:17][CH:18]=[C:14]3[C:8]3([CH2:13][CH2:12][NH:11][CH2:10][CH2:9]3)[O:7][C:6]=2[CH:19]=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>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:15]3[CH:16]=[CH:17][CH:18]=[C:14]3[C:8]3([CH2:13][CH2:12][N:11]([C:23]([C:22]4[CH:26]=[C:27]([O:30][CH3:31])[CH:28]=[CH:29][C:21]=4[F:20])=[O:24])[CH2:10][CH2:9]3)[O:7][C:6]=2[CH:19]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27745432-Fluoro-5-methoxybenzoic acidHCID 585513057'-Chlorospiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

7-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). 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-735246783c584b0f8d8665c40120d9d0
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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