Dimethylformamide → HCID 86660256, compound

HRID 1908058Notes

Reaction equation

HRID 1908058 reaction equation
[CH3:1][C:2]1[CH:26]=[CH:25][C:5]2[N:6]3[CH:24]=[CH:23][CH:22]=[C:7]3[C:8]3([CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]3)[O:9][C:4]=2[CH:3]=1.Cl[S:28](N=C=O)(=[O:30])=[O:29].C[N:35]([CH:37]=[O:38])C.C1C[O:42][CH2:41]C1>>[CH3:41][O:42][S:28]([NH:35][C:37]([C:24]1[N:6]2[C:7]([C:8]3([CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16])[CH2:11][CH2:10]3)[O:9][C:4]3[CH:3]=[C:2]([CH3:1])[CH:26]=[CH:25][C:5]=32)=[CH:22][CH:23]=1)=[O:38])(=[O:29])=[O:30]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8028Tetrahydrofuran2×HCID 70918Chlorosulfonyl isocyanateHCID 58550931HCID 58550931, compound

Product 1

HCID 86660256HCID 86660256, compoundYield 24%

Procedure

To tert-butyl 7′-methylspiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-carboxylate (5.0 g, 14.1 mmol) in THF (150 mL) at −78° C. was added dropwise chlorosulfonyl isocyanate (1.5 mL, 16.9 mmol) in THF (50 mL) over a period of 10 minutes. The mixture was stirred at that temperature for 4 hours and then DMF (3.5 mL, 45.9 mmol) was added dropwise and the mixture allowed to stir at room temperature overnight. The mixture was concentrated, diluted with DCM (500 mL) and washed with sat. NaHCO3 (200 mL), brine (200 mL), dried over MgSO4 and evaporated to yield a crude residue that was purified by column chromatography (50-100% dichloromethane/hexane) to give tert-butyl 1′-(methoxysulfonylcarbamoyl)-7′-methyl-spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-carboxylate as a pale yellow oil (1.3 g, 24%). 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J=8.0 Hz, 1H), 6.98 (d, J=4.0 Hz, 1H), 6.96-6.88 (m, 2H), 6.05 (d, J=4.0 Hz, 1H), 4.09-3.95 (m, 2H), 3.31-3.15 (m, 2H), 2.35 (s, 3H), 2.04 (d, J=14.0 Hz, 2H), 1.92-1.79 (m, 2H), 1.48 (s, 9H). ESI-MS m/z calc. 379.5. found 380.1 (M+1)+; Retention time 2.20 minutes (3 min run), and 7-methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbonitrile (0.5 g, 12%). 1H NMR (400 MHz, DMSO) δ 8.40 (s, 1H), 7.88 (d, J=8.3 Hz, 1H), 7.33 (d, J=4.1 Hz, 1H), 7.17 (s, 1H), 7.06 (d, J=8.4 Hz, 1H), 6.42 (d, J=4.1 Hz, 1H), 3.26-3.09 (m, 4H), 2.33 (s, 3H), 2.19-2.04 (m, 4H). ESI-MS m/z calc. 279.3. found 280.3 (M+1)+; Retention time 1.12 minutes (3 min run).

Workup

  1. stirringto stir at room temperature overnight
  2. concentrationThe mixture was concentrated
  3. additiondiluted with DCM (500 mL)
  4. washwashed with sat. NaHCO3 (200 mL), brine (200 mL)
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customto yield a crude residue that
  8. customwas purified by column chromatography (50-100% dichloromethane/hexane)

Sources & evidence

ORD record
ord-4fea9c48b35149709c26b7e6f50541ea
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

Loading…