Trimethyl orthoformate → HCID 67513684, compound

HRID 473919Notes

Reaction equation

HRID 473919 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[CH:11][C:12]3[O:18][CH2:17][CH2:16][N:15]([C:19]([N:21]4[CH:26]5[CH2:27][CH2:28][CH:22]4[CH2:23][C:24]([C:30]([F:33])([F:32])[F:31])([OH:29])[CH2:25]5)=[O:20])[CH2:14][C:13]=3[CH:34]=2)[CH:5]=[N:6][C:7]=1[NH2:8].[CH:35](OC)(OC)OC>C(OCC)C>[NH:1]1[C:2]2[C:7](=[N:6][CH:5]=[C:4]([C:9]3[CH:10]=[CH:11][C:12]4[O:18][CH2:17][CH2:16][N:15]([C:19]([N:21]5[CH:22]6[CH2:28][CH2:27][CH:26]5[CH2:25][C:24]([C:30]([F:33])([F:32])[F:31])([OH:29])[CH2:23]6)=[O:20])[CH2:14][C:13]=4[CH:34]=3)[CH:3]=2)[N:8]=[CH:35]1

Participants

4

Reactant 2

HCID 9005Trimethyl orthoformateHCID 67513726HCID 67513726, compound

Product 1

HCID 67513684HCID 67513684, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A slurry of 8-{[7-(5,6-diaminopyridin-3-yl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]carbonyl}-3-(trifluoromethyl)-8-azabicyclo[3.2.1]octan-3-ol (0.22 g, 0.46 mmol) and trimethyl orthoformate (3.5 mL) was heated (105° C.) for 30 minutes. The reaction mixture was diluted with ethyl ether and the resulting precipitate was collected by filtration. Purification by preparative reverse phase HPLC provided 8-{[7-(1H-imidazo[4,5-b]pyridin-6-yl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]carbonyl}-3-(trifluoromethyl)-8-azabicyclo[3.2.1]octan-3-ol (64 mg, 29% yield) as a white solid. 1H NMR (400 MHz, d6-DMSO) δ 9.39 (s, 1H), 8.87 (s, 1H), 8.44 (s, 1H), 7.66 (s, 1H), 7.62 (dd, 1H), 7.07 (d, 1H), 5.81 (bs, 1H), 4.57 (s, 2H), 4.26 (s, 2H), 4.05 (s, 2H), 3.70 (s, 2H), 2.03 (m, 4H), 1.74 (m, 4H); MS (ES) for C24H24F3N5O3: 488 (MH+).

Workup

  1. filtrationthe resulting precipitate was collected by filtration
  2. customPurification by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-573f82c01b924eb7bd1531c1defb9621
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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