10-ethoxy-14-methoxy-N-methyl-20-(trifluoromethyl)-9-oxa-4,5,16,18,22,25,28-heptaaza-10-phosphapentacyclo[21.2.2.212,15.12,5.117,21]hentriaconta-1(25),2(31),3,12,14,17(28),18,20,23,26,29-undecaene-24-carboxamide 10-oxide → 10-hydroxy-14-methoxy-N-methyl-20-(trifluoromethyl)-9-oxa-4,5,16,18,22,25,28-heptaaza-10-phosphapentacyclo[21.2.2.212,15.12,5.117,21]hentriaconta-1(25),2(31),3,12,14,17(28),18,20,23,26,29-undecaene-24-carboxamide 10-oxide

HRID 2279898Notes

Reaction equation

HRID 2279898 reaction equation
C([O:3][P:4]1(=[O:45])[CH2:28][C:27]2[CH:29]=[CH:30][C:24](=[C:25]([O:31][CH3:32])[CH:26]=2)[NH:23][C:22]2=[N:33][C:18](=[C:19]([C:34]([F:37])([F:36])[F:35])[CH:20]=[N:21]2)[NH:17][C:16]2[CH:38]=[CH:39][C:13](=[N:14][C:15]=2[C:40]([NH:42][CH3:43])=[O:41])[C:12]2=[CH:44][N:9]([N:10]=[CH:11]2)[CH2:8][CH2:7][CH2:6][O:5]1)C>Cl>[OH:45][P:4]1(=[O:3])[CH2:28][C:27]2[CH:29]=[CH:30][C:24](=[C:25]([O:31][CH3:32])[CH:26]=2)[NH:23][C:22]2=[N:33][C:18](=[C:19]([C:34]([F:36])([F:35])[F:37])[CH:20]=[N:21]2)[NH:17][C:16]2[CH:38]=[CH:39][C:13](=[N:14][C:15]=2[C:40]([NH:42][CH3:43])=[O:41])[C:12]2=[CH:44][N:9]([N:10]=[CH:11]2)[CH2:8][CH2:7][CH2:6][O:5]1

Participants

3

Reactant 1

HCID 7651826710-ethoxy-14-methoxy-N-methyl-20-(trifluoromethyl)-9-oxa-4,5,16,18,22,25,28-heptaaza-10-phosphapentacyclo[21.2.2.212,15.12,5.117,21]hentriaconta-1(25),2(31),3,12,14,17(28),18,20,23,26,29-undecaene-24-carboxamide 10-oxide

Product 1

HCID 8669783310-hydroxy-14-methoxy-N-methyl-20-(trifluoromethyl)-9-oxa-4,5,16,18,22,25,28-heptaaza-10-phosphapentacyclo[21.2.2.212,15.12,5.117,21]hentriaconta-1(25),2(31),3,12,14,17(28),18,20,23,26,29-undecaene-24-carboxamide 10-oxide

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A solution 10-ethoxy-14-methoxy-N-methyl-20-(trifluoromethyl)-9-oxa-4,5,16,18,22,25,28-heptaaza-10-phosphapentacyclo[21.2.2.212,15.12,5.117,21]hentriaconta-1(25),2(31),3,12,14,17(28),18,20,23,26,29-undecaene-24-carboxamide 10-oxide (Example 6, 30.0 mg, 0.0464 mmol) in concentrated HCl (6.0 mL) was stirred at 50° C. for 72 hours. The reaction mixture was concentrated under reduced pressure to a yellow foam. The material was purified on a Teledyne ISCO Combiflash® Rf system using a reverse phase column with Water/MeOH (100:0→0:100) as eluent to afford the title compound as 7.5 mg of a white solid (26%). 1H NMR (400 MHz, CD3OD): δ=8.41 (br. s., 1H), 8.31 (s, 1H), 8.27 (br. s., 1H), 7.87 (d, J=6.6 Hz, 1H), 7.59 (d, J=6.6 Hz, 1H), 7.45 (d, J=6.6 Hz, 1H), 6.70 (br. s., 1H), 6.27 (d, J=4.8 Hz, 1H), 4.42 (br. s., 2H), 3.83 (br. s., 3H), 3.52 (br. s., 2H), 2.93 (s, 3H), 2.80 (d, J=17.4 Hz, 2H), 2.16 (br. s., 2H). MS (ESI): m/z 619.17 [M+H]+. UPLC: tR=0.80 min (polar—2 min).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure to a yellow foam
  2. customThe material was purified on a Teledyne ISCO Combiflash® Rf system

Sources & evidence

ORD record
ord-35a95d65dd194b17aa5b87e8c1439ad2
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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