Diethyl (4-{[4-chloro-5-(trifluoromethyl) pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate → HCID 178476870, compound

HRID 1948042Notes

Reaction equation

HRID 1948042 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21](Cl)[C:20]([C:24]([F:27])([F:26])[F:25])=[CH:19][N:18]=2)=[C:12]([O:28][CH3:29])[CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[NH2:30][C:31]1[C:32]([C:44]([NH:46][CH3:47])=[O:45])=[N:33][C:34]([C@H:37]2[CH2:42][CH2:41][C@H:40]([OH:43])[CH2:39][CH2:38]2)=[CH:35][CH:36]=1>O>[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:30][C:31]3[C:32]([C:44](=[O:45])[NH:46][CH3:47])=[N:33][C:34]([C@H:37]4[CH2:38][CH2:39][C@H:40]([OH:43])[CH2:41][CH2:42]4)=[CH:35][CH:36]=3)[C:20]([C:24]([F:27])([F:26])[F:25])=[CH:19][N:18]=2)=[C:12]([O:28][CH3:29])[CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]

Participants

4

Reactant 2

HCID 86654002Diethyl (4-{[4-chloro-5-(trifluoromethyl) pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonateHCID 178485584HCID 178485584, compound

Product 1

HCID 178476870HCID 178476870, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The title compound was prepared according to the procedure for Example 231 using diethyl(4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (44.9 mg, 0.0989 mmol) and 3-amino-6-(trans-4-hydroxycyclohexyl)-N-methylpyridine-2-carboxamide (Example 232A, 37 mg, 0.15 mmol). The reaction mixture was poured into water and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered, concentrated and purified on an ISCO CombiFlash system (eluting with 0-4% MeOH/DCM) to isolate, after concentrating the relevant fractions and drying in vacuo, the desired product as 44.5 mg of a white solid. 1H NMR (400 MHz, DMSO-d6) d 1.20 (t, J=7.07 Hz, 6H), 1.23-1.33 (m, 2H), 1.59-1.72 (m, 2H), 1.77-1.86 (m, 2H), 1.94 (dd, J=13.01, 3.66 Hz, 2H), 2.56-2.67 (m, 1H), 2.83 (d, J=4.80 Hz, 3H), 3.28 (d, J=17.94 Hz, 2H), 3.45-3.55 (m, 1H), 3.74 (s, 3H), 3.94-4.04 (m, 4H), 4.57 (d, J=4.29 Hz, 1H), 6.89 (ddd, J=8.02, 2.27, 2.08 Hz, 1H), 7.05 (s, 1H), 7.35 (d, J=8.84 Hz, 1H), 7.41 (br. s., 1H), 8.38 (s, 1H), 8.88-8.95 (m, 1H), 9.01 (br. s., 1H), 12.33 (s, 1H). HRMS (ES+): m/z=667.2100 (100) [M+1]. HPLC: tR=1.50 min (ZQ2, polar—3 min).

Workup

  1. extractionextracted twice with EtOAc
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified on an ISCO CombiFlash system (eluting with 0-4% MeOH/DCM)
  6. customto isolate
  7. concentrationafter concentrating the relevant fractions
  8. customdrying in vacuo
  9. customHPLC: tR=1.50 min (ZQ2, polar—3 min)

Sources & evidence

ORD record
ord-73d7833ba7ea4bc9a7b7cea7f1b4fd06
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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