Formic Acid → Trifluoroacetic acid

HRID 1948066Notes

Reaction equation

HRID 1948066 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]([NH:23][C:24]3[CH:32]=[CH:31][C:30]([C:33]4[CH2:34][CH2:35][NH:36][CH2:37][CH:38]=4)=[C:29]4[C:25]=3[C:26](=[O:40])[N:27]([CH3:39])[CH2:28]4)[C:20]([C:41]([F:44])([F:43])[F:42])=[CH:19][N:18]=2)=[CH:12][CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[CH:45]([OH:47])=[O:46].C=O.C([BH3-])#N.[Na+]>CO>[CH2:6]([O:5][P:4]([CH2:9][C:10]1[CH:11]=[CH:12][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:32]=[CH:31][C:30]([C:33]4[CH2:34][CH2:35][N:36]([CH3:45])[CH2:37][CH:38]=4)=[C:29]4[C:25]=3[C:26](=[O:40])[N:27]([CH3:39])[CH2:28]4)[C:20]([C:41]([F:43])([F:44])[F:42])=[CH:19][N:18]=2)=[CH:14][CH:15]=1)(=[O:8])[O:3][CH2:1][CH3:2])[CH3:7].[F:42][C:41]([F:44])([F:43])[C:45]([OH:47])=[O:46]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 58292933HCID 58292933, compound

Product 2

HCID 6422Trifluoroacetic acidYield 403.9%HCID 58293043HCID 58293043, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Diethyl(4-{[4-{[2-methyl-3-oxo-7-(1,2,3,6-tetrahydropyridin-4-yl)-2,3-dihydro-1H-isoindol-4-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (Example 246, 20.0 mg, 0.0317 mmol), formic acid (5 uL, 0.1 mmol) and formaldehyde (3.0 uL, 0.11 mmol) were mixed in methanol (1.0 mL) at room temperature for 30 minutes. Sodium cyanoborohydride (20.0 mg, 0.318 mmol) was added and the mixture was stirred at room temperature overnight. The crude mixture was purified by MDP to obtain the title compound as a trifluoroacetic acid salt (7.3 mg, 35.7% yield). 1H NMR (400 MHz, methanol-d4) δ=1.27 (t, J=7.1 Hz, 6H), 2.87 (br. s., 1H), 2.93 (br. s., 1H), 3.05 (s, 3H), 3.19 (s, 3H), 3.29 (d, J=21.5 Hz, 2H), 3.36-3.46 (m, 1H), 3.73 (br. s., 1H), 3.80-3.90 (m, 1H), 4.00-4.16 (m, 5H), 4.59 (s, 2H), 5.95-6.04 (m, 1H), 7.34 (dd, J=8.6, 2.5 Hz, 2H), 7.50 (d, J=8.6 Hz, 1H), 7.58 (d, J=8.1 Hz, 2H), 8.36-8.43 (m, 1H), 8.75 (br. s., 1H). MS (ES+): m/z 645.23 (100) [MH+]; HPLC: tR=0.69 min (UPLC, purity).

Workup

  1. customThe crude mixture was purified by MDP

Sources & evidence

ORD record
ord-61e3f01fff0a45a89581b1bea4075e0f
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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