Methane → Methyl 4-[5-({2-[(4-{[ethoxy(hydroxy)phosphoryl]methyl}-2-methoxyphenyl)amino]-5-(trifluoromethyl)pyrimidin-4-yl}amino)-6-(methylcarbamoyl)pyridin-2-yl]-1-(3-hydroxypropyl)-1H-pyrrole-2-carboxylate

HRID 2279821Notes

Reaction equation

HRID 2279821 reaction equation
C([O:8][CH2:9][CH2:10][CH2:11][N:12]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][C:20]([NH:23][C:24]3[C:29]([C:30]([F:33])([F:32])[F:31])=[CH:28][N:27]=[C:26]([NH:34][C:35]4[CH:40]=[CH:39][C:38]([CH2:41][P:42]([O:45][CH2:46][CH3:47])([OH:44])=[O:43])=[CH:37][C:36]=4[O:48][CH3:49])[N:25]=3)=[C:19]([C:50](=[O:53])[NH:51][CH3:52])[N:18]=2)[CH:14]=[C:13]1[C:54]([O:56][CH3:57])=[O:55])C1C=CC=CC=1.C>CCO.[Pd]>[CH2:46]([O:45][P:42]([CH2:41][C:38]1[CH:39]=[CH:40][C:35]([NH:34][C:26]2[N:25]=[C:24]([NH:23][C:20]3[CH:21]=[CH:22][C:17]([C:15]4[CH:14]=[C:13]([C:54]([O:56][CH3:57])=[O:55])[N:12]([CH2:11][CH2:10][CH2:9][OH:8])[CH:16]=4)=[N:18][C:19]=3[C:50](=[O:53])[NH:51][CH3:52])[C:29]([C:30]([F:32])([F:33])[F:31])=[CH:28][N:27]=2)=[C:36]([O:48][CH3:49])[CH:37]=1)([OH:44])=[O:43])[CH3:47]

Participants

5

Reactant 2

HCID 297MethaneHCID 86697761methyl 1-[3-(benzyloxy)propyl]-4-[5-({2-[(4-{[ethoxy(hydroxy)phosphoryl]methyl}-2-methoxyphenyl)amino]-5-(trifluoromethyl)pyrimidin-4-yl}amino)-6-(methylcarbamoyl)pyridin-2-yl]-1H-pyrrole-2-carboxylate2×

Product 1

HCID 86697760Methyl 4-[5-({2-[(4-{[ethoxy(hydroxy)phosphoryl]methyl}-2-methoxyphenyl)amino]-5-(trifluoromethyl)pyrimidin-4-yl}amino)-6-(methylcarbamoyl)pyridin-2-yl]-1-(3-hydroxypropyl)-1H-pyrrole-2-carboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of methyl 1-[3-(benzyloxy)propyl]-4-[5-({2-[(4-{[ethoxy(hydroxy)phosphoryl]methyl}-2-methoxyphenyl)amino]-5-(trifluoromethyl)pyrimidin-4-yl}amino)-6-(methylcarbamoyl)pyridin-2-yl]-1H-pyrrole-2-carboxylate (Compound 38B, 582 mg, 0.717 mmol) and Palladium 10% wt. on Calcium Carbonate:Carbon black (63.4 mg, 0.031 mmol) in EtOH (11.4 mL), was evacuated and purged with d with H2(g) (3×) and left to stir overnight at rt for 16 hrs. The reaction mixture was filtered and concentrated in vacuo to a 330 mg of a solid which was used without further purification (64%). 1H NMR (400 MHz, CD3OD) δ 8.88-9.02 (m, 1H), 8.27 (s, 1H), 7.89 (s, 1H), 7.72 (d, J=6.3 Hz, 1H), 7.56-7.62 (m, 1H), 7.52 (d, J=1.5 Hz, 1H), 7.09 (s, 1H), 6.91 (d, J=8.1 Hz, 1H), 4.47 (t, J=6.8 Hz, 2H), 3.85-3.92 (m, 5H), 3.85 (br. s., 3H), 3.54-3.61 (m, 2H), 3.03 (d, J=22.0 Hz, 2H), 2.95-2.99 (m, 3H), 1.97-2.06 (m, 2H), 1.17 (t, J=7.1 Hz, 3H). MS (ESI): m/z=722.60 [M+H]+. UPLC: tR=1.22 min (UPLC-TOF: polar—2 min).

Workup

  1. custompurged with d with H2(g) (3×)
  2. waitleft
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated in vacuo to a 330 mg of a solid which
  5. customwas used without further purification (64%)
  6. customtR=1.22 min (UPLC-TOF: polar—2 min)

Sources & evidence

ORD record
ord-c8dba982becb416cab171ed3892b8d5f
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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