Trimethyl orthoformate → (s)-1-(4-((2-(2-Aminopyrimidin-5-yl)-4-(3-methylmorpholino)thieno[3,2-d]pyrimidin-6-yl)methyl)-1,4-diazepan-1-yl)ethanone

HRID 391153Notes

Reaction equation

HRID 391153 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]2[CH3:19])[C:5]2[S:10][C:9]([CH:11]=O)=[CH:8][C:6]=2[N:7]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[C:34]([N:37]1[CH2:43][CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)(=[O:36])[CH3:35].COC(OC)OC.[NH2:51][C:52]1[N:57]=[CH:56][C:55](B2OC(C)(C)C(C)(C)O2)=[CH:54][N:53]=1.CC([O-])=O.[K+]>O.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC#N.ClCCCl.CC(O)=O>[NH2:51][C:52]1[N:57]=[CH:56][C:55]([C:2]2[N:3]=[C:4]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]3[CH3:19])[C:5]3[S:10][C:9]([CH2:11][N:40]4[CH2:41][CH2:42][CH2:43][N:37]([C:34](=[O:36])[CH3:35])[CH2:38][CH2:39]4)=[CH:8][C:6]=3[N:7]=2)=[CH:54][N:53]=1

Participants

13

Reactant 6

HCID 9005Trimethyl orthoformateHCID 517044Potassium AcetateHCID 4186202N-AcetylhomopiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 58234096(S)-2-chloro-4-(3-methylmorpholino)thieno[3,2-d]pyrimidine-6-carbaldehyde

Product 1

HCID 24948166(s)-1-(4-((2-(2-Aminopyrimidin-5-yl)-4-(3-methylmorpholino)thieno[3,2-d]pyrimidin-6-yl)methyl)-1,4-diazepan-1-yl)ethanone

Reagents, catalysts & solvents 6

HCID 178418397HCID 178418397, compoundCatalystHCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Following General Procedure D, (S)-2-chloro-4-(3-methylmorpholino)thieno[3,2-d]pyrimidine-6-carbaldehyde (110 mg, 0.37 mmol), HOAc (22 mg), NaBH(OAc)3 (101 mg, 0.48 mmol), N-acetylhomopiperazine (63 mg, 0.44 mmol), 1,2-dichloroethane (1.0 mL), trimethylorthoformate were reacted at room temperature for 2 h. The crude product was used in the next step without purification. MS (Q1) 424 (M)+. Following general procedure A: crude product from above, 2-aminopyrimidine-5-boronic acid pinacol ester (106 mg, 0.48 mmol), Pd(PPh3)4 (30 mg), MeCN (1.5 mL) and 1M KOAc in H2O (1.5 mL) were irradiated at 140° C. for 30 min. The reaction mixture was diluted with CH2Cl2, and filtered. The filtrate was concentrated to give crude 425 which was purified by reverse phase HPLC (68 mg). MS (Q1) 483 (M)+

Workup

  1. customwere reacted at room temperature for 2 h
  2. customThe crude product was used in the next step without purification
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. customto give crude 425 which
  6. customwas purified by reverse phase HPLC (68 mg)

Sources & evidence

ORD record
ord-fe2d0ba438ef49c29b58532db39ab604
Source dataset
uspto-grants-2013_02
Patent number
US08383620B2

Reaction notes

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