Trimethyl orthoformate → HCID 25214475, compound

HRID 132609Notes

Reaction equation

HRID 132609 reaction equation
[CH2:1]1[C:10]2[C:5](=[C:6]([O:11][C:12]3[C:17]([NH:18][C:19]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=4)=[O:20])=[CH:16][CH:15]=[CH:14][N:13]=3)[CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.[CH:33]1([CH:39]=O)[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1.COC(OC)OC.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C>CO.C(O)(=O)C.CN1C(=O)CCC1>[CH:33]1([CH2:39][N:2]2[CH2:3][CH2:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][C:6]=3[O:11][C:12]3[C:17]([NH:18][C:19]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:30])[F:31])=[CH:24][CH:23]=4)=[O:20])=[CH:16][CH:15]=[CH:14][N:13]=3)[CH2:1]2)[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1

Participants

8

Reactant 4

HCID 9005Trimethyl orthoformateHCID 16275CyclohexanecarboxaldehydeHCID 2724942TriacetoxyborohydrideHCID 68533081HCID 68533081, compound

Product 1

HCID 25214475HCID 25214475, compoundYield 29.4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 1-(2-(1,2,3,4-tetrahydroisoquinolin-5-yloxy)pyridin-3-yl)-3-(4-(trifluoromethoxy)phenyl)urea (238f, 15 mg, 0.034 mmol), cyclohexanecarboxaldehyde (38 mg, 034 mmol), acetic acid (50 μL) were added to NMP (0.75 mL) and trimethylorthoformate (0.5 mL) and stirred at rt for 2.5 h. Triacetoxyborohydride (36 mg) was added and stirring was continued for 18 h. A solution of acetic acid in methanol (50% v/v, 0.5 mL) was added and reation mixture was directly purified on preparative HPLC to yield the desired material (5.4 mg). (M+H)+=541. 1H NMR (400 MHz, DMSO-D6) δ ppm 1.6-1.9 (m, 10H), 2.32 (m, 1H), 3.04-3.06 (m, 2 H), 3.66-3.75 (m, 2 H), 4.31-4.43 (m, 2 H), 4.60-4.70 (m, 2 H), 7.11 (dd, J=7.83, 4.80 Hz, 1 H), 7.18 (t, J=7.83 Hz, 2 H), 7.33 (d, J=8.08 Hz, 2 H), 7.39 (t, J=7.83 Hz, 1 H), 7.56 (d, J=9.09 Hz, 2 H), 7.65 (dd, J=4.80, 1.76 Hz, 1H), 8.53 (d, J=7.84 Hz, 1 H), 8.78 (s, 1 H), 9.54 (s, 1 H).

Workup

  1. stirringstirring
  2. waitwas continued for 18 h
  3. customreation mixture was directly purified on preparative HPLC

Sources & evidence

ORD record
ord-7a2b3addb7a5412c8eead3ade6b4890a
Source dataset
uspto-grants-2008_06
Patent number
US07388021B2

Reaction notes

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