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

HRID 511474Notes

Reaction equation

HRID 511474 reaction equation
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][C:14]=2[O:28][CH3:29])[N:3]=1.[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>[OH:43][C@H:40]1[CH2:41][CH2:42][C@H:37]([C:34]2[N:33]=[C:32]([C:44](=[O:45])[NH:46][CH3:47])[C:31]([NH:30][C:2]3[C:7]([C:8]([F:10])([F:9])[F:11])=[CH:6][N:5]=[C:4]([NH:12][C:13]4[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:19][CH2:20][CH3:21])[O:22][CH2:23][CH3:24])=[CH:15][C:14]=4[O:28][CH3:29])[N:3]=3)=[CH:36][CH:35]=2)[CH2:38][CH2:39]1

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) δ 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-b5d6c6458d994cf09676af061409f486
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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