Hydrochloric Acid → N-[4-[[(2,4-Diaminopyrido[2,3-d]pyrimidin-6-yl)methyl]methylamino]benzoyl]-L-glutamic acid

HRID 1248978

Reaction equation

HRID 1248978 reaction equation
[CH:1]1[C:6]([C:7]([NH:9][C@H:10]([C:16]([OH:18])=[O:17])[CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[O:8])=[CH:5][CH:4]=[C:3]([NH:19][CH2:20][C:21]2[CH:26]=[C:25]3[C:27]([NH2:32])=[N:28][C:29]([NH2:31])=[N:30][C:24]3=[N:23][CH:22]=2)[CH:2]=1.[OH-].[Na+].C=O.[BH3-][C:38]#N.[Na+].Cl>O=O>[NH2:31][C:29]1[N:28]=[C:27]([NH2:32])[C:25]2[CH:26]=[C:21]([CH2:20][N:19]([CH3:38])[C:3]3[CH:2]=[CH:1][C:6]([C:7]([NH:9][C@H:10]([C:16]([OH:18])=[O:17])[CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[O:8])=[CH:5][CH:4]=3)[CH:22]=[N:23][C:24]=2[N:30]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 972725-DeazaaminopterinHCID 5003444Sodium cyanoborohydride

Product 1

HCID 12908480N-[4-[[(2,4-Diaminopyrido[2,3-d]pyrimidin-6-yl)methyl]methylamino]benzoyl]-L-glutamic acid

Reagents, catalysts & solvents 1

HCID 977OxygenSolvent

Procedure

A suspension of Compound II (R=H) (100 mg, 0.211 mmol) in O2 free water (5 ml) under N2 was adjusted to pH 6.4 with 1N NaOH to give a solution which was treated with 38% HCHO (83.1 μl, 1.14 mmol) followed by NaBH3CN (19.9 mg, 0.317 mmol). The solution was maintained at pH 6.4 by gradual addition of 1N HCl over a period of 45 minutes. The solution was stirred under N2 for 23 hours, filtered and acidified to pH 3.6 with 1N HCl. The product was collected by filtration, washed with water at pH 3.6 and dried in vacuo (P2O5): yield 97 mg (94%, mp indefinite (softens and darkens above 217° C.); mass spectrum, m/e 454 (M+1)+ ; λmax nm (εx 10-3): 0.1N HCl-221 (37.1), 311 (19.0); pH 7-219 (35.1), 247 (18.1), 305 (25.2); 0.1N NaOH-249 (19.9), 305 (25.0), 355 sh (6.15; 1H-NMR (DMSO-d6, <5% w/v), δ2.00 m (CH2CH2CO), 2.28 t (CH2CO), 3.12 s (CH3), 4.32 m (CHN), 4.66 s (CH2N), 6.78 d, 7.72 d (C6H4), 8.31 d (5-CH), 8.59 d (7-CH).

Workup

  1. customto give a solution which
  2. filtrationfiltered
  3. filtrationThe product was collected by filtration
  4. washwashed with water at pH 3.6
  5. dry with materialdried in vacuo (P2O5)
  6. custom94%, mp indefinite (softens and darkens above 217° C.)
  7. wait1H-NMR (DMSO-d6, <5% w/v), δ2.00 m (CH2CH2CO), 2.28 t (CH2CO), 3.12 s (CH3), 4.32 m (CHN), 4.66 s (CH2N), 6.78 d, 7.72 d
  8. custom(C6H4), 8.31 d (5-CH), 8.59 d (7-CH)

Sources & evidence

ORD record
ord-60b27b7831fd48f7bb79d2104b4a745c
Source dataset
uspto-grants-1986_12
Patent number
US04628089

Linked notes

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