Diphosgene → HCID 178455381, compound

HRID 715570Notes

Reaction equation

HRID 715570 reaction equation
[Si:1]([O:8][C@H:9]1[C@H:13]2[O:14][CH2:15][C@@H:16]([O:17][C:18]3[N:40]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C:21]4=[N:22][C:23]([C:27]5[CH:32]=[CH:31][C:30]([C@@H:33]6[CH2:38][CH2:37][C@H:36]([NH2:39])[CH2:35][CH2:34]6)=[CH:29][CH:28]=5)=[C:24]([Cl:26])[CH:25]=[C:20]4[N:19]=3)[C@H:12]2[O:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[O:49]=[C:50](Cl)[O:51][C:52](Cl)(Cl)Cl.[O:57]1[CH2:62][CH2:61]C(O)[CH2:59][CH2:58]1>C1(C)C=CC=CC=1>[Si:1]([O:8][C@H:9]1[C@H:13]2[O:14][CH2:15][C@@H:16]([O:17][C:18]3[N:40]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C:21]4=[N:22][C:23]([C:27]5[CH:32]=[CH:31][C:30]([C@@H:33]6[CH2:38][CH2:37][C@H:36]([NH:39][C:50](=[O:49])[O:51][CH:52]7[CH2:61][CH2:62][O:57][CH2:58][CH2:59]7)[CH2:35][CH2:34]6)=[CH:29][CH:28]=5)=[C:24]([Cl:26])[CH:25]=[C:20]4[N:19]=3)[C@H:12]2[O:11][CH2:10]1)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10426DiphosgeneHCID 74956Tetrahydro-4H-pyran-4-olHCID 178455377HCID 178455377, compound

Product 1

HCID 178455381HCID 178455381, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
60 °C

Procedure

(cis)-4-(4-(2-((3R,3aR,6R,6aS)-6-(tert-Butyldimethylsilyloxy)hexahydrofuro[3,2-b]-furan-3-yloxy)-6-chloro-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-b]pyridin-5-yl)phenyl)cyclohexanamine (40 mg) is dissolved in toluene (2 mL), treated dropwise with a solution of diphosgene (6.8 μL) in toluene (2 mL), stirred for 10 minutes at room temperature and for 1.5 hours at 60° C. Then tetrahydro-2H-pyran-4-ol (5.3 μL) is added and the mixture is stirred for 48 hours at 60° C. The mixture is partitioned between ethylacetate and saturated aqueous NH4Cl solution. The organic phase is dried (MgSO4) and concentrated. The crude product is used directly in the next step.

Workup

  1. stirringthe mixture is stirred for 48 hours at 60° C
  2. customThe mixture is partitioned between ethylacetate and saturated aqueous NH4Cl solution
  3. dry with materialThe organic phase is dried (MgSO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-c69e16bf0fdb4ab18bf44d3854f5ab20
Source dataset
uspto-grants-2015_11
Patent number
US09187477B2

Reaction notes

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