Formaldehyde → HCID 178483320, compound

HRID 1013010Notes

Reaction equation

HRID 1013010 reaction equation
[CH2:1]([N:8]([CH2:16][CH2:17][C:18]1[N:23]=[C:22]([C:24]([NH:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)=[O:25])[C:21]([OH:35])=[C:20]([OH:36])[N:19]=1)[C:9](=O)OC(C)(C)C)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C=O.C([BH3-])#N.[Na+]>ClCCl.FC(F)(F)C(O)=O.C(O)(=O)C>[CH2:1]([N:8]([CH3:9])[CH2:16][CH2:17][C:18]1[N:23]=[C:22]([C:24]([NH:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)=[O:25])[C:21]([OH:35])=[C:20]([OH:36])[N:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 178453347HCID 178453347, compound

Product 1

HCID 178483320HCID 178483320, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

Crude tert-butyl benzyl[2-(4-{[(4-fluorobenzyl)amino]carbonyl}-5,6-dihydroxypyrimidin-2-yl)ethyl]carbamate (prepared as described in Step 3) was taken in dichloromethane/trifluoroacetic acid (8/2 v/v) and the mixture was stirred 1 hour at room temperature. After evaporation of volatiles, the crude organic product was taken in methanol and treated with triethyl amine (1 equivalent), formaldehyde (2 equivalents), sodium cyanoborohydride (1.2 equivalents) and acetic acid (pH=5.5). The mixture was stirred at room temperature for 1 hour. Volatiles were evaporated and product was purified by RP HPLC (C18, 5 μM, H2O/MeCN with 1% of TFA as eluant). Lyophilization of appropriate fractions gave the title compound (TFA salt) as a white solid. 1H NMR (400 MHz, d6-DMS) δ 12.78 (bs, 1H), 12.32 (bs, 1H), 9.5-9.4 (m, 2H), 7.48 (s, 5H), 7.42-7.32 (m, 2H), 7.12 (t, J=8.7 Hz, 2H), 4.59-4.45 (m, 3H), 4.23 (bs, 1H), 3.75 (bs, 1H), 3.52 (bs, 1H), 3.08-3.00 (m, 2H), 2.72 (s, 3H); MS (ES) C22H23FN4O3 requires 410. Found: 411 (M+H+).

Workup

  1. customAfter evaporation of volatiles
  2. stirringThe mixture was stirred at room temperature for 1 hour
  3. customVolatiles were evaporated
  4. customproduct was purified by RP HPLC (C18, 5 μM, H2O/MeCN with 1% of TFA as eluant)

Sources & evidence

ORD record
ord-4aad16af28f143ff99c22337f400581b
Source dataset
uspto-grants-2011_07
Patent number
US07981879B2

Reaction notes

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