Formic Acid → Trifluoroacetic acid

HRID 511497Notes

Reaction equation

HRID 511497 reaction equation
[CH3:1][N:2]1[C:10](=[O:11])[C:9]2[C:4](=[C:5]([C:39]3[CH2:40][CH2:41][NH:42][CH2:43][CH:44]=3)[CH:6]=[CH:7][C:8]=2[NH:12][C:13]2[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:38]=[CH:37][C:27]([CH2:28][P:29](=[O:36])([O:33][CH2:34][CH3:35])[O:30][CH2:31][CH3:32])=[CH:26][CH:25]=3)[N:14]=2)[CH2:3]1.[CH:45]([OH:47])=[O:46].C=O.C([BH3-])#N.[Na+]>CO>[CH3:1][N:2]1[C:10](=[O:11])[C:9]2[C:4](=[C:5]([C:39]3[CH2:40][CH2:41][N:42]([CH3:45])[CH2:43][CH:44]=3)[CH:6]=[CH:7][C:8]=2[NH:12][C:13]2[C:18]([C:19]([F:21])([F:22])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:38]=[CH:37][C:27]([CH2:28][P:29](=[O:36])([O:33][CH2:34][CH3:35])[O:30][CH2:31][CH3:32])=[CH:26][CH:25]=3)[N:14]=2)[CH2:3]1.[F:20][C:19]([F:22])([F:21])[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, 6 H), 2.87 (br. s., 1 H), 2.93 (br. s., 1 H), 3.05 (s, 3 H), 3.19 (s, 3 H), 3.29 (d, J=21.5 Hz, 2 H), 3.36-3.46 (m, 1 H), 3.73 (br. s., 1 H), 3.80-3.90 (m, 1 H), 4.00-4.16 (m, 5 H), 4.59 (s, 2 H), 5.95-6.04 (m, 1 H), 7.34 (dd, J=8.6, 2.5 Hz, 2 H), 7.50 (d, J=8.6 Hz, 1 H), 7.58 (d, J=8.1 Hz, 2 H), 8.36-8.43 (m, 1 H), 8.75 (br. s., 1 H). 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-cc83a7f7caea48d190171798ba2c1291
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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