Triethylamine → HCID 89721857, compound

HRID 2273079Notes

Reaction equation

HRID 2273079 reaction equation
ClC(Cl)(O[C:5](=[O:11])[O:6][C:7](Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:30]3[C:29](=[O:31])[N:28]([CH2:32][CH3:33])[CH2:27][C:26]([CH3:35])([CH3:34])[O:25][C:24]=3[N:23]=[C:22]([N:36]3[CH2:42][CH:41]4[O:43][CH:38]([CH2:39][CH2:40]4)[CH2:37]3)[N:21]=2)=[CH:16][C:15]=1[F:44].C(N(CC)CC)C.[CH2:52](O)[C@@H:53]([OH:55])C>C(Cl)Cl.O>[OH:55][C@@H:53]([CH3:52])[CH2:7][O:6][C:5](=[O:11])[NH:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:30]3[C:29](=[O:31])[N:28]([CH2:32][CH3:33])[CH2:27][C:26]([CH3:34])([CH3:35])[O:25][C:24]=3[N:23]=[C:22]([N:36]3[CH2:37][CH:38]4[O:43][CH:41]([CH2:40][CH2:39]4)[CH2:42]3)[N:21]=2)=[CH:16][C:15]=1[F:44]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 439846(S)-propane-1,2-diolHCID 89714851HCID 89714851, compound

Product 1

HCID 89721857HCID 89721857, compoundYield 49.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 134.43 mg (0.45 mmol) of triphosgene, 200 mg (0.45 mmol) of 4-(4-amino-3-fluorophenyl)-6-ethyl-8,8-dimethyl-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-7,8-dihydro-6H-9-oxa-1,3,6-triazabenzocyclohepten-5-one and 275.04 mg (2.72 mmol) of triethylamine in 50 ml of DCM is stirred at room temperature for 30 minutes. 134 mg (1.81 mmol) of (S)-propane-1,2-diol are added and the mixture is stirred for 2 hours at room temperature. The resulting mixture is hydrolysed with 5 ml of water and then evaporated under reduced pressure. The product is precipitated by addition of ethyl acetate/water. The product is filtered off and dried under vacuum to give 120 mg {4-[6-ethyl-8,8-dimethyl-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-5-oxo-5,6,7,8-tetrahydro-9-oxa-1,3,6-triazabenzocyclohepten-4-yl]-2-fluorophenyl}carbamic acid (S)-2-hydroxypropyl ester.

Workup

  1. stirringthe mixture is stirred for 2 hours at room temperature
  2. customevaporated under reduced pressure
  3. customThe product is precipitated by addition of ethyl acetate/water
  4. filtrationThe product is filtered off
  5. customdried under vacuum

Sources & evidence

ORD record
ord-3850fade43434f8892852e6c182c65ce
Source dataset
uspto-grants-2015_09
Patent number
US09120812B2

Reaction notes

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