Hydrochloric Acid → (S)-3-(3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(2-(dibutylamino)pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)benzamide

HRID 529040Notes

Reaction equation

HRID 529040 reaction equation
[CH2:1]([N:5]([CH2:37][CH2:38][CH2:39][CH3:40])[C:6]1[N:11]=[C:10]([C:12]2[CH:20]=[CH:19][C:18]([C:21](=[O:36])[NH:22][S:23]([C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH:27]=3)(=[O:25])=[O:24])=[CH:17][C:13]=2[C:14](O)=[O:15])[CH:9]=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4].[N:41]([CH2:44][C@@H:45]1[CH2:54][C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH2:47][NH:46]1)=[N+]=[N-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH-].[Na+].Cl>C1COCC1>[NH2:41][CH2:44][C@@H:45]1[CH2:54][C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH2:47][N:46]1[C:14]([C:13]1[CH:17]=[C:18]([CH:19]=[CH:20][C:12]=1[C:10]1[CH:9]=[CH:8][N:7]=[C:6]([N:5]([CH2:37][CH2:38][CH2:39][CH3:40])[CH2:1][CH2:2][CH2:3][CH3:4])[N:11]=1)[C:21]([NH:22][S:23]([C:26]1[CH:35]=[CH:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=1)(=[O:25])=[O:24])=[O:36])=[O:15]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 710607202-(2-(Dibutylamino)pyrimidin-4-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoic acid2×HCID 86718892(S)-3-(Azidomethyl)-1,2,3,4-tetrahydroisoquinoline2×

Product 1

HCID 70690001(S)-3-(3-(Aminomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(2-(dibutylamino)pyrimidin-4-yl)-N-(naphthalen-2-ylsulfonyl)benzamideYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Following a procedure analogous to that for the synthesis of Example 303, 2-(2-(dibutylamino)pyrimidin-4-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoic acid (Intermediate 303E, 25 mg, 0.05 mmol) was reacted with ((S)-3-(azidomethyl)-1,2,3,4-tetrahydroisoquinoline (Intermediate 92A, 11 mg, 0.06 mmol) and provided a crude oil which was dissolved in THF (1.1 mL). PPh3 (10 mg, 0.014 mmol) was added followed by aq. 0.5N NaOH (100 μL). The resulting reaction mixture was stirred at 50° C. for 1.5 h and then neutralized with 1N HCl solution (100 μL). The volatiles were removed in vacuo, and the residue was purified by preparative HPLC to give the title compound (5 mg, 52%). MS(ESI+) m/z 705.2 (M+H)+.

Workup

  1. customprovided a crude oil which
  2. customThe resulting reaction mixture
  3. customThe volatiles were removed in vacuo
  4. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-00e16baba92e4c6e94a5955220834a15
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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