Hydrochloric Acid → HCID 68182969, compound

HRID 1618336Notes

Reaction equation

HRID 1618336 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([NH:11][C:12]3[N:17]=[C:16]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])[N:15]=[C:14]([NH:24][C:25]4[CH:49]=[CH:48][C:28]([C:29]([NH:31][C@H:32]5[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C@H:34]([C:44]([O:46]C)=[O:45])[CH2:33]5)=[O:30])=[CH:27][CH:26]=4)[N:13]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Li+].[OH-].O.Cl>C1COCC1.CCOC(C)=O>[C:40]([O:39][C:37]([N:35]1[CH2:36][C@@H:32]([NH:31][C:29](=[O:30])[C:28]2[CH:48]=[CH:49][C:25]([NH:24][C:14]3[N:13]=[C:12]([NH:11][C:8]4([C:5]5[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=5)[CH2:9][CH2:10]4)[N:17]=[C:16]([O:18][CH2:19][C:20]([F:21])([F:23])[F:22])[N:15]=3)=[CH:26][CH:27]=2)[CH2:33][C@@H:34]1[C:44]([OH:46])=[O:45])=[O:38])([CH3:43])([CH3:41])[CH3:42]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 3939Lithium HydroxideHCID 68182819HCID 68182819, compound

Product 1

HCID 68182969HCID 68182969, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2S,4R)-1-tert-butyl 2-methyl 4-(4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzamido)pyrrolidine-1,2-dicarboxylate (500 mg, 0.708 mmol), was dissolved in THF (Ratio: 1.000, Volume: 4 mL) followed by the addition of LiOH (85 mg, 3.54 mmol) and Water (Ratio: 1.000, Volume: 4). The reaction was headed to 65° C. for 2 h. The reaction was diluted with EtOAc and acidified with 1N HCl. The organic layer was collected, washed with brine, dried over sodium sulfate, and concentrated under vacuum to give (2R,4S)-1-(tert-butoxycarbonyl)-4-(4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzamido)pyrrolidine-2-carboxylic acid (490 mg) which was used in the next step without further purification. 1H NMR (400 MHz, MeOD) δ ppm 1.33-1.41 (m, 4H), 1.45 (s, 9H), 2.28-2.49 (m, 2H), 3.40-3.47 (m, 1H), 3.85 (dd, J=10.7, 6.9 Hz, 1H), 4.33-4.47 (m, 1H), 4.60-4.72 (m, 1H), 4.86-4.93 (m, 2H), 7.20-7.32 (m, 4H), 7.59-7.71 (m, 3H), 7.77-7.89 (m, 1H); LC-MS (Condition A), MS m/z (M++H) 692.0.

Workup

  1. customThe organic layer was collected
  2. washwashed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-59e9e8e0ca884054835466625626b9fe
Source dataset
uspto-grants-2014_07
Patent number
US08765944B2

Reaction notes

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