Diisopropylethylamine → HCID 178476854, compound

HRID 511515Notes

Reaction equation

HRID 511515 reaction equation
CCCP(O)(O)=O.CCN(C(C)C)C(C)C.[CH2:17]([O:19][P:20]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33]2[N:38]=[C:37]([NH:39][C:40]3[CH:41]=[CH:42][C:43]([C@@H:51]4[CH2:56][CH2:55][C@H:54]([C:57]([OH:59])=O)[CH2:53][CH2:52]4)=[C:44]4[C:48]=3[C:47](=[O:49])[N:46]([CH3:50])[CH2:45]4)[C:36]([C:60]([F:63])([F:62])[F:61])=[CH:35][N:34]=2)=[C:28]([O:64][CH3:65])[CH:27]=1)([O:22][CH2:23][CH3:24])=[O:21])[CH3:18].Cl.[NH2:67][OH:68]>CN(C=O)C>[OH:68][NH:67][C:57]([C@@H:54]1[CH2:55][CH2:56][C@H:51]([C:43]2[CH:42]=[CH:41][C:40]([NH:39][C:37]3[C:36]([C:60]([F:63])([F:61])[F:62])=[CH:35][N:34]=[C:33]([NH:32][C:29]4[CH:30]=[CH:31][C:26]([CH2:25][P:20](=[O:21])([O:19][CH2:17][CH3:18])[O:22][CH2:23][CH3:24])=[CH:27][C:28]=4[O:64][CH3:65])[N:38]=3)=[C:48]3[C:44]=2[CH2:45][N:46]([CH3:50])[C:47]3=[O:49])[CH2:52][CH2:53]1)=[O:59]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 204484Propylphosphonic acidHCID 443297Hydroxyamine hydrochlorideHCID 178476855HCID 178476855, compound

Product 1

HCID 178476854HCID 178476854, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To 50% 1-propylphosphonic acid cyclic anhydride in DMF (9.9 μL, 0.017 mmol) were added additional DMF (0.5 mL), DIPEA (9.9 μL, 0.0567 mmol) and cis-4-(7-{[2-({4-[(diethoxyphosphoryl)methyl]-2-methoxyphenyl}amino)-5-(trifluoromethyl) pyrimidin-4-yl]amino}-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohexanecarboxylic acid (10.0 mg, 0.0142 mmol). The mixture was stirred at room temperature for 30 minutes. Hydroxylamine hydrochloride (2.0 mg, 0.0283 mmol) was added and the mixture was stirred at room temperature overnight. The crude mixture was purified by MDP to obtain the title compound (5.2 mg, 51% yield). 1H NMR (400 MHz, methanol-d4) d ppm 1.29 (t, J=7.1 Hz, 6 H), 1.68-1.82 (m, 4 H), 2.00-2.16 (m, 4 H), 2.52 (br. s., 1 H), 2.73 (t, J=11.1 Hz, 1 H), 3.19 (s, 3 H), 3.38 (d, J=21.7 Hz, 2 H), 3.90 (s, 3 H), 4.11 (qd, J=7.3, 7.1 Hz, 4 H), 4.55 (s, 2 H), 6.95-7.04 (m, 1 H), 7.14 (s, 1 H), 7.39 (br. s., 1 H), 7.65 (d, J=8.1 Hz, 1 H), 8.33 (br. s., 2 H). MS (ES+): m/z 721.19 (100) [MH+]; HPLC: tR=0.97 min (UPLC, purity).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. customThe crude mixture was purified by MDP

Sources & evidence

ORD record
ord-90731f63ea8d487c8ab727df601b38ae
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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