Hydrogen Bromide → HCID 87352808, compound

HRID 705609Notes

Reaction equation

HRID 705609 reaction equation
C(OC([N:11]1[CH2:15][CH:14]2[CH2:16][CH:17]([CH2:19][O:20][C:21]3[CH:30]=[C:29]4[C:24]([C:25]([O:31][C:32]5[CH:37]=[CH:36][C:35]([NH:38][C:39]([NH:41][C:42](=[O:50])[CH2:43][C:44]6[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=6)=[S:40])=[CH:34][C:33]=5[F:51])=[N:26][CH:27]=[N:28]4)=[CH:23][C:22]=3[O:52][CH3:53])[CH2:18][CH:13]2[CH2:12]1)=O)C1C=CC=CC=1.[BrH:54]>CC(O)=O.CCOCC>[BrH:54].[BrH:54].[F:51][C:33]1[CH:34]=[C:35]([NH:38][C:39]([NH:41][C:42](=[O:50])[CH2:43][C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)=[S:40])[CH:36]=[CH:37][C:32]=1[O:31][C:25]1[C:24]2[C:29](=[CH:30][C:21]([O:20][CH2:19][CH:17]3[CH2:18][CH:13]4[CH2:12][NH:11][CH2:15][CH:14]4[CH2:16]3)=[C:22]([O:52][CH3:53])[CH:23]=2)[N:28]=[CH:27][N:26]=1

Participants

5

Reactant 2

HCID 260Hydrogen BromideHCID 866298685-{4-[2-Fluoro-4-(3-phenylacetyl-thioureido)-phenoxy]-6-methoxy-quinazolin-7-yloxymethyl}-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid benzyl ester

Product 1

HCID 87352808HCID 87352808, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

5-{4-[2-Fluoro-4-(3-phenylacetyl-thioureido)phenoxy]-6-methoxy-quinazolin-7-yloxymethyl}-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid benzyl ester (3.3 g, 4.5 mmol) was dissolved in AcOH (70 ml) to which was added 33% HBr in AcOH (12 ml). The reaction mixture was stirred at room temperature for 1 hr. diluted with Et2O (1000 ml) and the resulting solids filtered, washed with Et2O, and dried under high vacuum to give the 1-{3-fluoro-4-[6-methoxy-7-(octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinazolin-4-yloxy]-phenyl}-3-phenylacetyl-thiourea, dihydrobromide salt (3.4 g, 100%). 1H-NMR (400 MHz, DMSO): 12.42 (s, 1H), 11.80 (s, 1H), 8.84 (br s, 2H), 8.64 (s, 1H), 7.92 (m, 1H), 7.59 (s, 1H), 7.49 (m, 2H), 7.41 (s, 1H), 7.33 (m, 4H), 7.27 (m, 1H), 4.17 (d, 2H), 3.95 (s, 3H), 3.73 (s, 2H), 3.17 (m, 2H), 3.10 (m, 2H), 2.83 (m, 2H), 2.45 (m, 1H), 2.15 (m, 2H), 1.30 (m, 2H). LC/MS Calcd for [M+H]+ 602.2. found 602.1.

Workup

  1. filtrationthe resulting solids filtered
  2. washwashed with Et2O
  3. customdried under high vacuum

Sources & evidence

ORD record
ord-9db4367f78304ac48d564ea3c72a9e47
Source dataset
uspto-grants-2015_11
Patent number
US09174947B2

Reaction notes

Loading…